Pathogenesis Of Cardiovascular Disease Research Articles

Visceral fat and cardiometabolic future in children and adolescents: a critical update.

Cardiovascular disease (CVD) is a process whose pathogenetic mechanisms start very early in life. Recently, the importance of visceral adipose tissue (VAT) has been highlighted in the development of CVD. VAT does not always depend on body mass index (BMI) and has been implicated in unfavorable metabolic activity and cardiovascular adverse events. Abnormally high deposition of VAT is associated with metabolic syndrome, obesity-associated phenotype, and cardiometabolic risk factors. Although the importance of visceral fat has not been studied broadly or extensively in long-term studies in children and adolescents, it appears that it does not have the same behavior as in adults, it is related to the appearance of cardiac risk factors. In adolescents, it plays a role in the pathogenesis of CVD that occur later in adulthood. Excess body weight and adiposity may lead to the development of early myocardial and pathological coronary changes in childhood. The purpose of this review is to summarize the risk factors, the clinical significance, and the prognostic role of visceral obesity in children and adolescents. In addition, extensive reference is made to the most commonly used techniques for the evaluation of VAT in clinical settings. IMPACT: Visceral obesity, plays an important role in cardiovascular health from very early in an individual's life. Visceral adipose tissue (VAT) distribution is not entirely related to body mass index (BMI) and provides additional prognostic information. There is a need to pay more attention to the assessment of VAT in young people, to develop methods that would go beyond the measurement of only BMI in clinical practice and to identify individuals with excess visceral adiposity and perhaps to monitor its changes.

Major roles of the gut microbiota and microRNAs in cardiovascular disease events: a systematic review

Introduction: Gut microbiota (GM) is an essential mediator in the health of GM and has been identified as the origin of several diseases by influencing cell signaling and T cell receptor pathways in the central nervous system. Several microRNAs participate in signaling networks through GM intervention. The interaction between GM and miRNAs plays a crucial role in vascular dysfunction. GM can metabolize L-carnitine, choline, and phosphatidylcholine and produce vascular-toxic metabolites such as trimethylamine-Noxide (TMAO), which is associated with the atherosclerotic process. Nutrology and dietary therapy represent important strategies, especially with the use of plant-derived miRNAs to modify GM. Objective: To carry out a systematic review to highlight the main roles of the gut microbiota and microRNAs in cardiovascular disease events. Methods: The present study followed a concise systematic review model (PRISMA). The literary search process was carried out from March to May 2023 and was developed based on Scopus, PubMed, Science Direct, Scielo, and Google Scholar, using scientific articles from 2002 to 2022. The low quality of evidence was attributed to reports of cases, editorials, and brief communications, according to the GRADE instrument. The risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: The total of 126 studies were found for eligibility analysis, and then 42 of the 64 total studies were selected for this systematic review. According to the GRADE instrument, most studies showed homogeneity in their results, with X2 =88.7%>50%. It was concluded that the gut microbiota can be influenced by diet, genetics, and environmental factors. Changes in the microbial population can lead to multiple diseases, including cardiovascular disease. miRNAs have been known as important regulators of several biological functions, and are also involved in the pathogenesis of cardiovascular diseases. There is evidence that disturbances in the gut microbiota and derived metabolites impair the development of atherosclerotic cardiovascular disease. Studies have shown that YRNAs belonging to extracellular vesicles and their fragments play important roles in the initiation, progression, and diagnosis of atherosclerosis.

THE ROLE OF HOMOCYSTEINE IN THE PATHOGENESIS OF GYNECOLOGICAL DISEASES

Despite the fact that homocysteine was first described in 1932, at present, the study of changes in the synthesis and content of this amino acid reveals new mechanisms for the disease development. It should be mentioned that studies confirming the correlation between elevated homocysteine levels and human pathologies (cardiovascular diseases, pregnancy complications, neuropsychiatric disorders) have appeared only recently. This indicates that hyperhomocysteinemia has not been resolved and deserves clinicians’ and researchers’ attention.
 Most publications present studies on hyperhomocysteinemia as part of the pathogenesis of cardiovascular diseases. However, more recently, elevated homocysteine level has been considered as a marker in preeclampsia and postoperative thromboembolism, including that after reproductive surgery. It was noted that in early pregnancy the activation of endothelial cells is changed in women with hyperhomocysteinemia and uterine fibroids. It increases thrombosis risks, and later, during the chorion formation, an endothelial defect can cause fetoplacental insufficiency, and in case of endotheliosis progression lead to preeclampsia and eclampsia. In recent years, some authors associate hyperhomocysteinemia with disorders of the female reproductive system and ovulatory abilities, possible pathogenesis of benign tumors, pregnancy pathologies and delivery issues.
 A detailed study of elevated homocysteine in women can help in solving a number of issues, such as the role of hyperhopmocysteinemia in the pathogenesis of gynecological diseases and development of reproductive disorders. 
 There is much information on the role of homocysteine in the development of endothelial dysfunction and significant metabolic disorders. At the same time, there is not enough studies on the changes in folate metabolism, which cause hyperhomocysteinemia and directly affect the development of endocrine gynecological and obstetric pathologies. These problems require further analysis. The correlation between the hyperhomocysteinemia and development of gynecological pathologies is currently one of the promising scientific areas. Special attention is paid to the pathogenesis of uterine fibroids in terms of vascular theory. Despite ongoing research, there is only insufficient information on the role of excess homocysteine in the pathogenesis of uterine fibroids.

Oridonin supplementation attenuates atherosclerosis via NLRP-3 inflammasome pathway suppression.

Atherosclerosis, a long-term inflammatory and immune condition affecting medium- and large-sized arteries, results in the thickening of artery walls and the accumulation of inflammatory cells and fatty streaks that establish fibrous capsules with macrophages at the site of injury. Atherosclerosis has a major impact on the pathogenesis of cardiovascular diseases. Oridonin has been shown to exclusively inhibit the NLRP3 inflammasome without affecting the activation of AIM-2 or NLRC-4 inflammasomes. The current study aimed to evaluate how adding Oridonin to a diet impacts the onset of atherosclerosis. Twenty-one male rabbits weighing 1.5 to 2.0 kg were included in the study. The rabbits were kept in controlled environmental conditions and divided into three groups: a normal control group fed a conventional chow diet, an atherogenic control group fed a high-cholesterol diet (2% cholesterol-rich), and an Oridonin-treated group (Ori) fed an atherogenic diet supplemented with Oridonin (20 mg/kg) administered orally once daily. Compared to animals on a normal diet, an atherogenic diet was associated with a statistically significant (p=0.001) increase in the mean expression of the NLRP3 inflammasome mRNA. The Oridonin-treated group showed a statistically significant (p=0.001) decline in the mean expression of NLRP3 inflammasome mRNA compared to the atherogenic group. Furthermore, the initial atherosclerotic lesion in the group treated with Oridonin was statistically (p=0.001) less severe compared to the atherogenic group. Finally, Ori treated group had significantly (p≤0.001) lower IL-1B immunostaining intensity than the atherogenic group (mean rank 14.5,25 respectively). The study concluded that Oridonin supplementation resulted in less severe initial atherosclerotic lesions, likely due to the suppression of NLRP3 inflammasome and the anti-inflammatory effect through the downregulation of IL1B expression.

Molecular and Cellular Aspects of Endothelial-Mesenchymal Transition in Cardiovascular Diseases

Endothelial cells (ECs), which form the inner surface of the blood vessels, contact with blood, withstand mechanical pressure, and demonstrate heterogeneous reactions to exogenous and endogenous stimuli. ECs have unique properties in accordance with their niche, and play an important role in regulating vascular homeostasis. Endothelial cells may undergo a dynamic phenotypic switch in terms of its heterogeneity, which may lead to endothelial dysfunction and a number of associated pathologies. Endothelial-mesenchymal transition (EndMT) is one of the possible molecular and cellular mechanisms of such kind. EndMT is characterized by phenotypic changes in ECs through which the cells obtain new properties, i.e. start producing mesenchymal markers such as alpha-SMA and vimentin, change morphology, and become able to migrate. EndMT is a complex biological process, which may be induced by inflammation, hypoxia or oxidative stress, and be involved in pathogenesis of cardiovascular disease. This manuscript presents the key markers, inhibitors, inducers of endothelial-mesenchymal transition, and overall state-of-the-art of EndMT in cardiovascular diseases.

Review:Research status of cardiovascular and cerebrovascular diseases and non-coding RNA

Cardiovascular and cerebrovascular diseases (CVD) encompass a range of conditions affecting the heart, brain, and blood vessels, including coronary heart disease, hypertension, and stroke. In recent years, there has been growing evidence highlighting the significant role of non-coding RNAs (ncRNAs) in the development and progression of cardiovascular diseases. Among the various types of ncRNAs, long-stranded non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) have emerged as prominent players in cardiovascular research. Advancements in technology and in-depth research have revealed that ncRNAs and circRNAs exert regulatory effects on the biological functions of the cardiovascular system through various pathways. For instance, they can modulate the proliferation, migration, and apoptosis of vascular endothelial cells, as well as regulate cardiac muscle contraction and cardiomyocyte apoptosis. Additionally, ncRNAs and circRNAs can influence downstream targets and pathways involved in cardiovascular diseases. The exploration of ncRNAs and circRNAs in cardiovascular research has opened up new avenues for the diagnosis and treatment of CVDs. By understanding the intricate regulatory mechanisms mediated by these non-coding RNAs, researchers have gained valuable insights into the pathogenesis of cardiovascular diseases and identified potential therapeutic targets. Consequently, these studies have provided novel ideas and approaches for the diagnosis, prevention, and management of CVDs.

Regulatory Roles of MicroRNAs in the Pathogenesis of Metabolic Syndrome.

Metabolic syndrome refers to a group of several disease conditions together with high glucose triglyceride levels, high blood pressure, lower high-density lipoprotein level, and large waist circumference. About 400 million people worldwide, one-third of the Euro-American population and 27% Chinese population over age 50 have it. microRNAs, an abundant novel class of endogenous small, non-coding RNAs in eukaryotic cells, act as negative controllers of gene expression by promoting either degradation/translational repression of target messenger RNA. More than 2000 microRNAs in the human genome have been identified and they are implicated in various biological & pathophysiological processes, including glucose homeostasis, inflammatory response, and angiogenesis. Destruction of microRNAs has a crucial role in the pathogenesis of obesity, cardiovascular disease, and diabetes. Recently the discovery of circulating microRNAs in human serum may help to promote metabolic crosstalk between organs and serves as a novel approach for the identification of various diseases, like Type 2 diabetes & atherosclerosis. In this review, we will discuss the most recent and up-to-date research on the pathophysiology and histopathology of metabolic syndrome besides their historical background and epidemiological highlight. As well as search the methodologies employed in this field of research and the potential role of microRNAs as novel biomarkers and therapeutic targets for metabolic syndrome in the human body. Furthermore, the significance of microRNAs in promising strategies, like stem cell therapy, which holds enormous promise for regenerative medicine in the treatment of metabolic disorders will also be discussed.

Clinical utility of inflammatory and genetic biomarkers for cardiovascular disease prevention, categorization, and treatment.

The complex interplay of increased atherogenic lipoproteins, inflammation, and immune activation hallmarks the pathogenesis of atherosclerotic cardiovascular disease (ASCVD). Atherosclerotic cardiovascular disease remains a leading cause of death, yet risk estimator tools lack comprehensiveness for genetic/inflammatory biomarkers associated with ASCVD. Unexplained ASCVD risk necessitates a better understanding of primary, secondary, and tertiary prevention variables. This article discusses the clinical utility of genetic and inflammatory biomarkers for ASCVD risk prediction, management, treatment, and recategorization into primary, secondary, and tertiary prevention. Furthermore, nurse practitioners (NPs) should use a ternary prevention classification system instead of the current binary system to mitigate risk in the large group of patients with subclinical ASCVD. High-sensitivity C-reactive protein (hs-CRP)-linearly associated with ASCVD-and lipoprotein-associated phospholipase-A 2 (Lp-PLA 2 ) and myeloperoxidase (MPO), both associated with plaque vulnerability/rupture, are inflammatory biomarkers. Elevated hs-CRP, MPO, and Lp-PLA 2 treatment requires addressing root causes of elevation (e.g., obesity, insulin resistance, tobacco use, gingival disease, and chronic autoimmune/infectious conditions). In addition, haptoglobin (Hp) phenotype determines the antioxidant potential of Hp. Haptoglobin phenotype, a root cause of ASCVD, is a one-time test. Individuals with Hp 2-2 should adopt a gluten-free diet to reduce endothelial and intestinal inflammation. Nurse practitioners should use stricter glycemic goals (hemoglobin A1c ≤6.5%) and add daily vitamin E if this group has type 2 diabetes. Genetic/inflammatory biomarkers should be used to better predict ASCVD risk and tailor primary, secondary, and tertiary prevention treatment. Clinical use of these biomarkers reaches beyond the standard of care to reduce residual ASCVD risk.

Drug-gut Microbiome Interaction in Atherosclerosis Therapeutics.

Atherosclerosis (AS) is one of the major risk factors for cardiovascular disease pathogenesis, and current studies have found that the development of atherosclerosis is closely related to the intestinal microbiome. This review describes the relationship between the development of atherosclerosis and the gut microbiome with its metabolites and reviews the interactions between atherosclerosis-related drugs and the intestinal microbiome, especially the in vivo metabolic effects of the intestinal microbiome on drugs related to the treatment of atherosclerosis, to provide further understanding for the development of drugs based on the intestinal microbiome to treat atherosclerosis.

Association of Serum Oxysterols with Cholesterol Metabolism Markers and Clinical Factors in Patients with Coronary Artery Disease: A Covariance Structure Analysis.

Oxysterols have been implicated in the pathogenesis of cardiovascular diseases. Serum levels of oxysterols could be positively correlated with cholesterol absorption and synthesis. However, physiological regulation of various serum oxysterols is largely unknown. The aim of this study was to investigate the relationship between clinical factors and cholesterol metabolism markers, and identify oxysterols associated with cholesterol absorption and synthesis in patients with coronary artery disease. Subjects (n = 207) who underwent coronary stenting between 2011 and 2013 were studied cross-sectionally. We measured lipid profiles including serum oxysterols. As for the serum biomarkers of cholesterol synthesis and absorption, oxysterol levels were positively correlated with campesterol and lathosterol. Covariance structure analysis revealed that dyslipidemia and statin usage had a positive correlation with "cholesterol absorption". Statin usage also had a positive correlation with "cholesterol synthesis". Several oxysterols associated with cholesterol absorption and/or synthesis. In conclusion, we elucidated the potential clinical factors that may affect cholesterol metabolism, and the associations between various oxysterols with cholesterol absorption and/or synthesis in patients with coronary artery disease.

Distribution of Serum 25-Hydroxyvitamin D Levels in Hypertensive Heart Disease Patients with Atrial Fibrillation in a Secondary Medical Facility in Edo State, Nigeria

Vitamin D deficiency has been implicated in the pathogenesis of hypertension and other cardiovascular diseases which are common risk factors for atrial fibrillation (AF). It also exhibits anti-inflammatory and antioxidant properties. This study aimed to estimate the level of vitamin D in hypertensive heart disease patients who had atrial fibrillation.

Structure and properties of fibrin/polyvinyl alcohol interpenetrating polymer network hydrogel as a modifying coating for small-diameter vascular grafts

Background: Interpenetrating polymer network (IPN) hybrid hydrogels enable regulating their properties by varying the composition and concentration of their components. Fibrin is an available natural polymer with ideal biological properties but low strength and tendency to retraction. Polyvinyl alcohol hydrogels are stable, comparable in strength to biological tissues but bioinert. Fibrin/polyvinyl alcohol (F/PVA) IPN can overcome the shortcomings of each component and create an improved material for tissue engineering.Objective: To assess the possibility of and conditions for obtaining a homogeneous IPN by subsequent fibrin polymerization and polyvinyl alcohol cryostructuring while preserving as much as possible mechanical and biological properties beneficial for tissue engineering.Methods: F/PVA IPN was obtained by subsequent fibrin polymerization (30 mg/mL) and polyvinyl alcohol cryostructuring (15, 30, and 60 mg/mL). We studied the structure using a scanning electron microscope, histology, infrared spectroscopy, and X-ray diffraction analysis. We tested mechanical properties and shrinkage of the samples. Biological features were assessed in vitro in terms of viability, cell count, proliferative and metabolic activity of EA.hy926 endothelial cell culture.Results: Our study found the maximum amount of fibrin on the surface of F30PVA15 IPN and its minimum amount on the surface of F30PVA60. These results were supported by the high biological appeal of F30PVA15 compared with F30PVA30 and F30PVA60. F30PVA60 hydrogels demonstrated shrinkage resistance compared to the template; F30PVA30 and F30PVA15 samples decreased by 1.4 and 2.5 times, respectively. Although the mechanical strength of all monocomponent hydrogels and IPN samples did not compare to that of the internal thoracic vein, F30PVA30 and F30PVA60 demonstrated better results than F30PVA15 and fibrin alone.Conclusion: Our method allows obtaining shrink-resistant IPN hydrogels with improved mechanical and tolerable biological properties at polyvinyl alcohol concentrations of > 15 mg/mL and < 60 mg/mL. However, the insufficient strength of this material limits its use in vascular engineering to a modifying coating. Received 25 January 2023. Revised 17 March 2023. Accepted 29 March 2023. Funding: This research was funded by the complex program of basic research under the Siberian Branch of the Russian Academy of Sciences within the basic research topic of Research Institute for Complex Issues of Cardiovascular Diseases No. 0419-2022-0001 “Molecular, cellular and biomechanical mechanisms of the pathogenesis of cardiovascular diseases in the development of new treatment methods based on personalized pharmacotherapy, minimally invasive medical devices, biomaterials and tissue-engineered implants”. Conflict of interest: The authors declare no conflict of interest. Contribution of the authorsConception and study design: V.G. Matveeva, M.A. RezvovaData collection and analysis: V.G. Matveeva, M.A. Rezvova, T.V. Glushkova, E.O. Krivkina, A.V. SergeevaStatistical analysis: V.G. Matveeva, M.A. Rezvova, T.V. Glushkova, A.V. SergeevaDrafting the article: V.G. MatveevaCritical revision of the article: V.G. Matveeva, M.A. Rezvova, L.V. Antonova, L.S. BarbarashFinal approval of the version to be published: V.G. Matveeva, M.A. Rezvova, T.V. Glushkova, A.V. Sergeeva, E.O. Krivkina, L.V. Antonova, L.S. Barbarash

Increased CaMKII activation and contrast changes of cardiac β1-and β3-Adrenergic signaling pathways in a humanized angiotensinogen model of hypertension

AimsUpregulation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) contributes to the pathogenesis of cardiovascular disease, including hypertension. Transgenic rats expressing the human angiotensinogen gene [TGR (hAGT)L1623] are a new novel humanized model of hypertension that associates with declines in cardiac contractile function and β-adrenergic receptor (AR) reserve. The molecular mechanisms are unclear. We tested the hypothesis that in TGR (hAGT)L1623 rats, left ventricular (LV) myocyte CaMKIIδ and β3-AR are upregulated, but β1-AR is down-regulated, which are important causes of cardiac dysfunction and β-AR desensitization. Main methodsWe compared LV myocyte CaMKIIδ, CaMKIIδ phosphorylation (at Thr287) (pCaMKIIδ), and β1-and β3-AR expressions and determined myocyte functional and [Ca2+]I transient ([Ca2+]iT) responses to β-AR stimulation with and without pretreatment of myocytes using an inhibitor of CaMKII, KN-93 (10−6 M, 30 min) in male Sprague Dawley (SD; N = 10) control and TGR (hAGT)L1623 (N = 10) adult rats. Key findingsHypertension in TGR (hAGT)L1623 rats was accompanied by significantly increased LV myocyte β3-AR protein levels and reduced β1-AR protein levels. CaMKIIδ phosphorylation (at Thr287), pCaMKIIδ was significantly increased by 35%. These changes were followed by significantly reduced basal cell contraction (dL/dtmax), relaxation (dR/dtmax), and [Ca2+]iT. Isoproterenol (10−8 M) produced significantly smaller increases in dL/dtmax, dR/dtmax, and [Ca2+]iT. Moreover, only in TGR (hAGT)L1623 rats, pretreatment of LV myocytes with KN-93 (10−6 M, 30 min) fully restored normal basal and isoproterenol-stimulated myocyte contraction, relaxation, and [Ca2+]iT. SignificanceLV myocyte CaMKIIδ overactivation with associated contrast changes in β3-AR and β1-AR may be the key molecular mechanism for the abnormal contractile phenotype and β-AR desensitization in this humanized model of hypertension.

Long-Term Impacts of Preeclampsia on the Cardiovascular System of Mother and Offspring.

Preeclampsia is a pregnancy-specific complication that is associated with an increased postpartum risk of cardiovascular disease (CVD) in both women and their offspring, although the underlying mechanisms have yet to be fully elucidated. Nevertheless, differential methylation of cytosine-phosphate-guanosine islands and alterations in the expression of microRNA, associated with an elevated risk of CVD, have been observed in women and their children following preeclampsia. Among this specific population, genetic and epigenetic factors play crucial roles in the development of CVD in later life. A series of biomolecules involved in inflammation, oxidative stress, and angiogenesis may link pregnancy vascular bed disorders in preeclampsia to the pathogenesis of future CVD and thus could be valuable for the prediction and intervention of long-term CVD in women with a history of preeclampsia and their offspring. Here, we present insights into the cardiovascular structure and functional changes of women with a history of preeclampsia and their offspring. With a focus on various underlying mechanisms, the conclusions from this review are expected to provide more potential diagnostics and treatment strategies for clinical practice.

Plasma homocysteine levels and associated factors in community-dwelling adolescents: the EVA-TYROL study.

Homocysteine (Hcy) has been associated with an adverse cardiovascular risk profile in adolescents. Assessment of the association between plasma Hcy levels and clinical/laboratory factors might improve our understanding of the pathogenesis of cardiovascular disease. Hcy was measured in 1,900 14- to 19-year-old participants of prospective population-based EVA-TYROL Study (44.3% males, mean age 16.4 years) between 2015 and 2018. Factors associated with Hcy were assessed by physical examination, standardized interviews, and fasting blood analysis. Mean plasma Hcy was 11.3 ± 4.5 µmol/L. Distribution of Hcy was characterized by extreme right skew. Males exhibited higher Hcy and sex differences increased with increasing age. Univariate associations with Hcy emerged for age, sex, body mass index, high-density lipoprotein cholesterol, and for factors pertaining to blood pressure, glucose metabolism, renal function, and diet quality, whereas the most important multivariate predictors of Hcy were sex and creatinine. Clinical and laboratory factors associated with Hcy in adolescents were manifold, with sex and high creatinine identified as strongest independent determinants. These results may aid when interpreting future studies investigating the vascular risk of homocysteine.

Pleiotropic activities of succinate: The interplay between gut microbiota and cardiovascular diseases.

Cardiovascular diseases (CVDs) continue to be a significant contributor to global mortality, imposing a substantial burden and emphasizing the urgent need for disease control to save lives and prevent disability. With advancements in technology and scientific research, novel mechanisms underlying CVDs have been uncovered, leading to the exploration of promising treatment targets aimed at reducing the global burden of the disease. One of the most intriguing findings is the relationship between CVDs and gut microbiota, challenging the traditional understanding of CVDs mechanisms and introducing the concept of the gut-heart axis. The gut microbiota, through changes in microbial compositions and functions, plays a crucial role in influencing local and systemic effects on host physiology and disease development, with its metabolites acting as key regulators. In previous studies, we have emphasized the importance of specific metabolites such as betaine, putrescine, trimethylamine oxide, and N,N,N-trimethyl-5-aminovaleric acid in the potential treatment of CVDs. Particularly noteworthy is the gut microbiota-associated metabolite succinate, which has garnered significant attention due to its involvement in various pathophysiological pathways closely related to CVDs pathogenesis, including immunoinflammatory responses, oxidative stress, and energy metabolism. Furthermore, we have identified succinate as a potential biomarker, highlighting its therapeutic feasibility in managing aortic dissection and aneurysm. This review aims to comprehensively outline the characteristics of succinate, including its biosynthetic process, summarize the current evidence linking it to CVDs causation, and emphasize the host-microbial crosstalk involved in modulating CVDs. The insights presented here offer a novel paradigm for future management and control of CVDs.

The association between non-lipid metabolomic biomarkers and prognostically important left ventricular phenotypes

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): British Heart Foundation. Background Metabolomics is the detailed profiling of an individual’s circulating metabolites including carbohydrates, lipids, amino and fatty acids, and ketone bodies. Of all the -omics technologies, it provides the most proximal molecular fingerprint to clinical phenotypes and, in conjunction with large-scale population scale cohorts, can allow interrogation of alterations in metabolism that may contribute to cardiovascular disease pathogenesis prior to disease onset. Purpose Given the well-established role of lipids as an important cardiovascular risk factor, this study examines the association between non-lipid circulating metabolites and prognostically important CMR phenotypes in order to provide insight into biological mechanisms as well as identify potentially novel biomarkers. Methods This study used data from the UK Biobank; 31 non-lipid metabolites were measured. Outcome variables were LV end-diastolic volume, LV mass and LV ejection fraction. Metabolite biomarkers were log-transformed and were included in multivariate regression models with additional covariates: age, sex, ethnicity, height, BMI, hypertension, diabetes, hypercholesterolaemia, physical activity, smoking status and fasting time. Correction for multiple testing was performed using the Benjamini-Hochberg method. Results After exclusions and outlier removal, there were 10,769 participants included in the analysis. The mean age was 64 years and 52% of participants were female. Significant results are detailed in Table 1. There was evidence for associations between LV mass, end-diastolic volume and ejection fraction and circulating metabolites, in particular amino acids and fatty acids. Conclusions In the context of the limitations and biases inherent in observational analyses, this study suggests that non-lipid circulating metabolites may influence prognostically important CMR phenotypes. Further exploration, in particular through Mendelian randomisation which can suggest potentially causal associations, is required which may, in turn, provide further biological mechanistic insights into remodelling, as well as highlight potentially novel biomarkers.

#5000 DIFFERENCES IN CIRCULATING IMMUNE CELLS PROFILE BETWEEN MALES WITH CARDIORENAL SYNDROME TYPE II AND CKD PATIENTS WITHOUT CARDIOVASCULAR DISEASE

Abstract Background and Aims Maladaptive activation of the immune system plays an important role in the pathogenesis of cardiovascular disease (CVD) and chronic kidney disease (CKD). The immune system components can act as mediators of organ cross-talk and may be involved in the reciprocal dysfunction that occurs in cardiorenal syndromes (CRS). The aim of our study was to investigate potential differences in blood levels of specific immune cells subsets between a cohort of type II CRS patients and CKD patients without established CVD. Method 40 stable male patients with CRS type II and 30 male CKD patients without CVD, matched for eGFR (CKD-EPI) were enrolled in this cross-sectional study. Exclusion criteria were history of malignancy, autoimmunity and active or chronic infections. The peripheral blood immune cell subsets CD14++CD16-, CD14++CD16+ and CD14+CD16++ absolute values and percentages out of total monocytes and NK cells (CD3+CD16+56+), CD3-CD19+ B lymphocytes, CD3+ CD4+ T cells, CD3+CD8+ T cells and Tregs (CD4+CD25+FoxP3+) absolute values and percentages out of total lymphocytes were measured by flow cytometry. Simultaneously, clinical, laboratory and echocardiographic data were assessed. Multiple regression analyses to assess independent relationships were performed by building separate models with each of the immune cells as the dependent variable and respective univariate correlates including patient group. Results Mean age of patients with CRS and CKD was 72±10 versus 66±10 years respectively (p = 0.01), mean eGFR was 37±14 and 33±16ml/min/1.73 m2 respectively (p = 0.28) and median urinary protein to creatine ratio (UPCR) was 0.19 (IQR, 0.10-0.52) versus 1.03 (IQR, 0.17-2.09) gr protein/gr creatinine (p = 0.02) respectively. CRS patients displayed increased levels of pro-inflammatory, intermediate CD14++CD16+ monocytes [41 (IQR, 24-78)/µL] compared to their CKD counterparts [35 (IQR, 18-43)/µL] (p = 0.04). A higher Tregs percentage was found in CRS patients [2.7% (IQR, 2.0%-3.9%)] compared to CKD patients [2.0% (IQR, 1.6%-2.6%)] (p = 0.03). Lower mean levels of lymphocytes were observed in CRS patients (1557±691/µL) compared to the CKD cohort (1920±545/µL) (p = 0.04). Finally, CRS patients displayed lower NK cell counts [148 (IQR, 103-258)/µL] compared to CKD patients [324 (IQR, 179-368)/µL] (p = 0.001). Age and UPCR did not correlate with immune cells subsets in the whole cohort, neither in the two groups separately. At multivariate regression analysis, the differences in immune cells between the two groups remained statistically significant. Specifically, in patients with CRS the intermediate CD14++CD16+ monocytes counts correlated positively with CRP (p = 0.002) and ESR (p = 0.02). A positive correlation was found between eGFR and total lymphocytes (p = 0.009), T cells (p = 0.005) and CD4+ T cells (p = 0.005) counts. The number and percentage of nonclassical CD14+CD16++ monocytes were higher in CRS patients with left ventricular ejection fraction (LVEF) less than 30% compared to patients with LVEF above 30% [33 (IQR, 18-37)/µL versus 13 (IQR, 10-29)/µL (p = 0.02) and 4.5% (IQR, 3.4%-7.2%) versus 2.7% (IQR, 1.9%-5.4%) (p = 0.03) respectively]. With regard to etiology, patients with dilated cardiomyopathy compared to patients with ischemic CVD displayed increased counts of intermediate CD14++CD16+ monocytes [75 (IQR, 41-104)/µL versus 36 (IQR, 22-61)/µL (p = 0.01)] and non-classical CD14+CD16++ monocytes [37 (IQR, 35-49)/µL versus 21 (IQR, 12-32)/µL (p = 0.02)]. Finally, NK cells and Tregs levels were lower in patients with atrial fibrillation compared to those without [133 (IQR, 79-173)/µL versus 260 (IQR, 151-314)/µL (p = 0.01)] and [32 (IQR, 21-43)/µL vs 47 (IQR, 34-85)/µL (p = 0.006)] respectively. Conclusion Patients with CRS type II exhibit alterations of the immune cells subsets profile in the peripheral blood compared to CKD patients of similar kidney function but without CVD. Our findings suggest that distinct immune mechanisms might be involved in the pathogenesis or the chronic course of CRS type II as compared to CKD. Future research is required to evaluate their pathophysiological or prognostic significance.

Serum adiponectin profile in obese Bangladeshi children attending an obesity clinic

Background and objective: Childhood obesity plays major role in the pathogenesis of various cardiovascular and metabolic diseases. Serum adiponectin has been found to be associated with several cardiometabolic risk factors. The study investigated the serum adiponectin levels and its relationship with obesity and cardiometabolic risk factors in Bangladeshi obese children. Material and methods: Overweight or obese children, between 6-18 years of age, attending the obesity clinic of the Department of Endocrinology, BSMMU were enrolled. Waist circumference (WC) and blood pressure (BP) were measured and blood samples were taken for estimation of glucose, insulin, lipid profile and adiponectin. Fasting plasma glucose (FPG), serum insulin and lipid profile were estimated by automated analyzer. Insulin resistance (HOMA-IR) was calculated from fasting insulin and fasting plasma glucose values. Serum adiponectin (total) was measured by ELISA method using DRG ELISA kit, Germany. Results:A total of 78 overweight or obese children of 6-18-year of age were enrolled. The mean (±SD) age of the study population was 12.22 ± 2.56 years and the mean BMI was 28.79 ± 4.54 kg/m2. Mean (±SD) serum adiponectin was 36.93 ± 17.85 µg/ml in 78 overweight/obese children. One way ANOVA showed no significant (P= 0.582) difference of adiponectin levels among children with overweight and different grades of obesity. There was no significant correlation between adiponectin and measures of generalized (r=0.035, p=0.763) or central (r=0.098, p=0.392) obesity. Also, no significant correlation was found between serum adiponectin level and any of cardiovascular risk factors of obesity or metabolic health. Conclusion: The study showed high serum adiponectin level in obese Bangladeshi children. Also, no association was found between serum adiponectin levels with grades of obesity and cardiometabolic risk factors among obese children of Bangladesh. IMC J Med Sci. 2023; 17(2):009. DOI: https://doi.org/10.55010/imcjms.17.019 *Correspondence: Palash Chandra Sutradhar, Department of Medicine, Sir Salimullah Medical College Mitford Hospital, Kotwali, Dhaka-1000, Bangladesh. Email: palashdmc@gmail.com

Oxygen consumption rate to evaluate mitochondrial dysfunction and toxicity in cardiomyocytes.

The increase in the types and complexity of diseases has led to significant advances in diagnostic techniques and the availability of effective therapies. Recent studies have focused on the role of mitochondrial dysfunction in the pathogenesis of cardiovascular diseases (CVDs). Mitochondria are important organelles in cells that generate energy. Besides the production of adenosine triphosphate (ATP), the energy currency of cells, mitochondria are also involved in thermogenesis, control of intracellular calcium ions (Ca2+), apoptosis, regulation of reactive oxygen species (ROS), and inflammation. Mitochondrial dysfunction has been implicated in several diseases including cancer, diabetes, some genetic diseases, and neurogenerative and metabolic diseases. Furthermore, the cardiomyocytes of the heart are rich in mitochondria due to the large energy requirement for optimal cardiac function. One of the main causes of cardiac tissue injuries is believed to be mitochondrial dysfunction, which occurs via complicated pathways which have not yet been completely elucidated. There are various types of mitochondrial dysfunction including mitochondrial morphological change, unbalanced levels of substances to maintain mitochondria, mitochondrial damage by drugs, and mitochondrial deletion and synthesis errors. Most of mitochondrial dysfunctions are linked with symptoms and diseases, thus we focus on parts of mitochondrial dysfunction about fission and fusion in cardiomyocytes, and ways to understand the mechanism of cardiomyocyte damage by detecting oxygen consumption levels in the mitochondria.