Ischemic Cardiovascular Disease Research Articles

Ten-year prognosis of acute atrial fibrillation in ST-elevation myocardial infarction: recurrence and risk stroke.

Atrial fibrillation (AF) often complicates ST elevation acute myocardial infarction (STEMI), with associated risks including stroke and mortality. Anticoagulation therapy for these patients and AF prognosis remains controversial. The aim was to evaluate long-term prognosis of STEMI patients complicated with AF in the acute phase. We performed a retrospective analysis on a prospective register involving 4,184 patients admitted for STEMI to the intensive cardiac care unit of 2 tertiary centres from 2007 to 2015. Patients with pre-existing permanent AF were excluded. Out of these, 269 (6.4%) patients developed AF within the first 48 hours after STEMI and were matched with a control group based on age and left ventricular ejection fraction (LVEF). After matching, a total of 470 patients were included (n=235, AF-STEMI; n=235, control group). Mean age 69.0 years, and 31.7% women. No differences were found in gender, cardiovascular risk factors or ischemic heart disease. AF-STEMI patients experienced more sustained ventricular tachycardia, advanced atrioventricular block, heart failure, and cardiogenic shock. In-hospital mortality was also higher in AF-STEMI patients (11.9% vs 7.2%, p=0.008). After 10-years follow-up, the AF-STEMI group had remained with higher mortality (50.5% vs. 36.2%; p=0.003) and a greater recurrence of AF (44.2% vs. 14.7%; p<0.001), without differences in stroke incidence (10.1% vs. 9.3%). As a conclusion, patients with AF complicating STEMI have higher rates of heart failure, cardiogenic shock, and in-hospital mortality. After a 10-year follow-up, they exhibit a high risk of AF recurrence and mortality, with no significant differences in stroke incidence.

Time Series Forecasting of Cardiovascular Mortality: Machine Learning Based on State Economic and Local Medical Data.

This study focuses on the complex interplay of healthcare, economic factors, and population dynamics, addressing a research gap in regional-level models that integrate diverse features within a temporal framework. Our primary objective is to develop an advanced temporal model for predicting cardiovascular mortality in Russian regions by integrating global and local healthcare features with economic and population dynamics. Utilizing a dataset from the Almazov Center's Department of Mortality Performance Monitoring, covering 94 regions and 752 records from January 1, 2015, to December 31, 2023, our analysis incorporates key parameters such as angioplasty procedures, population morbidity rates, Ischemic Heart Disease (IHD) and Cardiovascular Diseases (CVD) monitoring, and demographic data. Employing XGBoost and a regression model, our methodology ensures the model's robustness and generalizability.

Waist-to-height ratio and body fat percentage as risk factors for ischemic cardiovascular disease: a prospective cohort study from UK Biobank

BackgroundThe independent effect of waist-to-height ratio (WHtR) and body fat percentage (BF%) on ischemic cardiovascular disease (CVD) remains uncertain. ObjectivesThis study aimed to investigate the independent associations of WHtR and BF% with ischemic CVD. MethodsThis prospective cohort study used data from the UK Biobank. BF% was calculated as fat mass divided by body weight, measured by bioimpedance. Cox models estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for overall and sex-specific associations of BF% and WHtR with risks of ischemic CVD and its main subtypes [myocardial infarction (MI) and ischemic stroke (IS)], adjusted for a range of potential confounders, including mutual adjustment for BF% and WHtR. ResultsIn total, 468,333 participants without existing CVD were included in the analysis. During 12 y of follow-up, 20,151 ischemic CVD events, 13,604 MIs, and 6681 ISs were recorded. WHtR was linearly associated with ischemic CVD, MI, and IS, with an HR per 5% increase of 1.23 (95% CI: 1.20, 1.25), 1.24 (95% CI: 1.21, 1.27), and 1.22 (95% CI: 1.18, 1.26), respectively, independent of BF%. A stronger association between WHtR and MI was seen in females than in males. The association of BF% with these outcomes was substantially attenuated in both sexes after adjustment for WHtR. For example, in females, the HR (highest compared with lowest fifth) was reduced from 1.94 (95% CI: 1.76, 2.15) to 1.04 (95% CI: 0.90, 1.01) for ischemic CVD, from 2.04 (95% CI: 1.79, 2.32) to 0.97 (95% CI: 0.81, 1.16) for MI, and from 1.81 (95% CI: 1.54, 2.13) to 1.07 (95% CI: 0.85, 1.33) for IS. ConclusionsWHtR, when used as a proxy measure for central obesity, is linearly associated with ischemic CVD in both sexes, which is independent of BF%. In contrast, the relationship of BF% with these health outcomes is predominantly driven by its correlation with WHtR.

Ten-year prognosis of acute atrial fibrillation in ST-elevation myocardial infarction: recurrence and stroke risk

Abstract Funding Acknowledgements None. Background Atrial fibrillation (AF) often complicates ST elevation acute myocardial infarction (STEMI), with associated risks including stroke and mortality. Anticoagulation therapy for these patients and AF prognosis remains controversial. The aim was to evaluate long-term prognosis of STEMI patients complicated with AF in the acute phase. Methods We performed a prospective register involving 4,184 patients admitted for STEMI to the intensive cardiac care unit of two tertiary centres from 2007 to 2015. Patients with pre-existing permanent AF were excluded. Out of these, 269 (6.4%) patients developed AF within the first 48 hours after STEMI and were matched with a control group based on age and left ventricular ejection fraction (LVEF). Results After matching, a total of 470 patients were included (n=235, AF-STEMI; n=235, control group). Mean age 69.0 years, and 31.7% women. No differences were found in gender, cardiovascular risk factors or ischemic heart disease. AF-STEMI patients experienced more sustained ventricular tachycardia (12.8% vs. 4.7%; p=0.003), advanced atrioventricular block (13.2% vs. 6.0%; p=0.012), heart failure (28.5% vs. 18.7%; p=0.017), and cardiogenic shock (17.4% vs. 8.5%; p=0.006). In-hospital mortality was also higher in AF-STEMI patients (11.9% vs 7.2%, p=0.008). After 10-years follow-up, the AF-STEMI group had remained with higher mortality (50.5% vs. 36.2%; p=0.003) and a greater recurrence of AF (44.2% vs. 14.7%; p&amp;lt;0.001), without differences in stroke incidence (10.1% vs. 9.3%). Conclusion Patients with AF complicating STEMI have higher rates of heart failure, cardiogenic shock, and in-hospital mortality. After a 10-years follow up, they exhibit a high risk of AF recurrence, with no significant differences in stroke incidence.Kaplan Meier curves

3D-Printed proangiogenic patches of photo-crosslinked gelatin and polyurethane hydrogels laden with vascular cells for treating vascular ischemic diseases

Engineering vascularized tissues remains a promising approach for treating ischemic cardiovascular diseases. The availability of 3D-bioprinted vascular grafts that induce therapeutic angiogenesis can help avoid necrosis and excision of ischemic tissues. Here, using a combination of living cells and biodegradable hydrogels, we fabricated 3D-printed biocompatible proangiogenic patches from endothelial cell-laden photo-crosslinked gelatin (EC-PCG) bioink and smooth muscle cell-encapsulated polyurethane (SMC-PU) bioink. Implantation of 3D-bioprinted proangiogenic patches in a mouse model showed that EC-PCG served as an angiogenic capillary bed, whereas patterned SMC-PU increased the density of microvessels. Moreover, the assembled patterns between EC-PCG and SMC-PU induced the geometrically guided generation of microvessels with blood perfusion. In a rodent model of hindlimb ischemia, the vascular patches rescued blood flow to distal tissues, prevented toe/foot necrosis, promoted muscle remodeling, and increased the capillary density, thereby improving the heat-escape behavior of ischemic animals. Thus, our 3D-printed vascular cell-laden bioinks constitute efficient and scalable biomaterials that facilitate the engineering of vascular patches capable of directing therapeutic angiogenesis for treating ischemic vascular diseases.

Hemodynamics of ventricular-arterial coupling under enhanced external counterpulsation: An optimized dual-source lumped parameter model

Background and objectiveEnhanced external counterpulsation (EECP) is a mechanically assisted circulation technique widely used in the rehabilitation and management of ischemic cardiovascular diseases. It contributes to cardiovascular functions by regulating the afterload of ventricle to improve hemodynamic effects, including increased diastolic blood pressure at aortic root, increased cardiac output and enhanced blood perfusion to multiple organs including coronary circulation. However, the effects of EECP on the coupling of the ventricle and the arterial system, termed ventricular-arterial coupling (VAC), remain elusive. We aimed to investigate the acute effect of EECP on the dynamic interaction between the left ventricle and its afterload of the arterial system from the perspective of ventricular output work. MethodsA neural network assisted optimization algorithm was proposed to identify the ordinary differential equation (ODE) relation between aortic root blood pressure and flow rate. Based on the optimized order of ODE, a lumped parameter model (LPM) under EECP was developed taking into consideration of the simultaneous action of cardiac and EECP pressure sources. The ventricular output work, in terms of aortic pressure and flow rate cooperated with the LPM, was used to characterize the VAC of ventricle and its afterload. The VAC subjected to the principle of minimal ventricular output work was validated by solving the Euler-Poisson equation of cost function, ultimately determining the waveforms of aortic pressure and flow rate. ResultsA third-order ODE can precisely describe the hemodynamic relationship between aortic pressure and flow rate. An optimized dual-source LPM with three energy-storage elements has been constructed, showing the potential in probing VAC under EECP. The LPM simulation results demonstrated that the VAC in terms of aortic pressure and flow rate yielded to the minimal ventricular output work under different EECP pressures. ConclusionsThe ventricular-arterial coupling under EECP is subjected to the minimal ventricular output work, which can serve as a criterion for determining aortic pressure and flow rate. This study provides insight for the understanding of VAC and has the potential in characterizing the performance of the ventricular and arterial system under EECP.

Impact of Age on Prescribing Patterns of Cardiovascular Medications in Older Japanese Patients with Non-Dialysis-Dependent Chronic Kidney Disease: A Cross-Sectional Study.

Older patients with chronic kidney disease (CKD) are more likely to be excluded from clinical trials. This exclusion affects the quality of cardiovascular disease (CVD) prevention in this population. Baseline data from the Fukuoka Kidney Disease Registry (FKR) cohort, which included 4476 adult patients with CKD stages G1-G5, were cross-sectionally analyzed to compare the use of recommended drugs for preventing CVD in each age group. Different prescribing patterns were observed according to age for the cardiovascular drug classes. Older patients with CKD were less likely to receive renin-angiotensin system (RAS) inhibitors and were more likely to receive calcium channel blockers. The proportion of anticoagulation prescriptions for patients with CKD and atrial fibrillation decreased in the older age group (≥ 75 years). However, the proportion of antiplatelet therapy in patients with ischemic CVD increased linearly with age, even in the very old group aged ≥ 85 years. These findings suggest a severe cardiovascular burden in patients with CKD. Notably, RAS inhibitor use was avoided in the older group despite a severe cardiovascular burden, such as a high prevalence of CVD history and massive albuminuria ＞300 mg/g creatinine. This finding indicates that an older age independently contributed to the non-use of RAS inhibitors, even after adjusting for other covariates. This study suggests that age is a potential barrier to the treatment of patients with CKD and highlights the need to establish individualized treatment strategies for cardiovascular protection in this population.

Modulation of atherosclerosis-related signaling pathways by Chinese herbal extracts: Recent evidence and perspectives.

Atherosclerotic cardiovascular disease remains a preeminent cause of morbidity and mortality globally. The onset of atherosclerosis underpins the emergence of ischemic cardiovascular diseases, including coronary heart disease (CHD). Its pathogenesis entails multiple factors such as inflammation, oxidative stress, apoptosis, vascular endothelial damage, foam cell formation, and platelet activation. Furthermore, it triggers the activation of diverse signaling pathways including Phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), NF-E2-related factor 2/antioxidant response element (Nrf2/ARE), the Notch signaling pathway, peroxisome proliferator-activated receptor (PPAR), nucleotide oligo-structural domain-like receptor thermoprotein structural domain-associated protein 3 (NLRP3), silencing information regulator 2-associated enzyme 1 (Sirt1), nuclear transcription factor-κB (NF-κB), Circular RNA (Circ RNA), MicroRNA (mi RNA), Transforming growth factor-β (TGF-β), and Janus kinase-signal transducer and activator of transcription (JAK/STAT). Over recent decades, therapeutic approaches for atherosclerosis have been dominated by the utilization of high-intensity statins to reduce lipid levels, despite significant adverse effects. Consequently, there is a growing interest in the development of safer and more efficacious drugs and therapeutic modalities. Traditional Chinese medicine (TCM) offers a vital strategy for the prevention and treatment of cardiovascular diseases. Numerous studies have detailed the mechanisms through which TCM active ingredients modulate signaling molecules and influence the atherosclerotic process. This article reviews the signaling pathways implicated in the pathogenesis of atherosclerosis and the advancements in research on TCM extracts for prevention and treatment, drawing on original articles from various databases including Google Scholar, Medline, CNKI, Scopus, and Pubmed. The objective is to furnish a reference for the clinical management of cardiovascular diseases.

Cardiovascular Disease from Pathophysiology to Risk Estimation: Is Inflammation Estimated through Perivascular Attenuation on Computed Tomography the Key?

(1) Background: Systemic inflammation stands as a well-established risk factor for ischemic cardiovascular disease, as well as a contributing factor in the development of cardiac arrhythmias, notably atrial fibrillation. Furthermore, scientific studies have brought to light the pivotal role of localized vascular inflammation in the initiation, progression, and destabilization of coronary atherosclerotic disease. (2) Methods: We comprehensively review recent, yet robust, scientific evidence elucidating the use of perivascular adipose tissue attenuation measurement on computed tomography applied to key anatomical sites. Specifically, the investigation extends to the internal carotid artery, aorta, left atrium, and coronary arteries. (3) Conclusions: The examination of perivascular adipose tissue attenuation emerges as a non-invasive and indirect means of estimating localized perivascular inflammation. This measure is quantified in Hounsfield units, indicative of the inflammatory response elicited by dense adipose tissue near the vessel or the atrium. Particularly noteworthy is its potential utility in assessing inflammatory processes within the coronary arteries, evaluating coronary microvascular dysfunction, appraising conditions within the aorta and carotid arteries, and discerning inflammatory states within the atria, especially in patients with atrial fibrillation. The widespread applicability of perivascular adipose tissue attenuation measurement underscores its significance as a diagnostic tool with considerable potential for enhancing our understanding and management of cardiovascular diseases.

Insights into the use of oxygen-ozone therapy in ischemic cardiopathy and cardiovascular disease: a role for mitochondria?

Insights into the use of oxygen-ozone therapy in ischemic cardiopathy and cardiovascular disease: a role for mitochondria?

Laminin Alpha 2 Enhances the Protective Effect of Exosomes on Human iPSC-Derived Cardiomyocytes in an In Vitro Ischemia-Reoxygenation Model.

Ischemic heart disease, a leading cause of death worldwide, manifests clinically as myocardial infarction. Contemporary therapies using mesenchymal stromal cells (MSCs) and their derivative (exosomes, EXOs) were developed to decrease the progression of cell damage during ischemic injury. Laminin alpha 2 (LAMA2) is an important extracellular matrix protein of the heart. Here, we generated MSC-derived exosomes cultivated under LAMA2 coating to enhance human-induced pluripotent stem cell (hiPSC)-cardiomyocyte recognition of LAMA2-EXOs, thus, increasing cell protection during ischemia reoxygenation. We mapped the mRNA content of LAMA2 and gelatin-EXOs and identified 798 genes that were differentially expressed, including genes associated with cardiac muscle development and extracellular matrix organization. Cells were treated with LAMA2-EXOs 2 h before a 4 h ischemia period (1% O2, 5% CO2, glucose-free media). LAMA2-EXOs had a two-fold protective effect compared to non-treatment on plasma membrane integrity and the apoptosis activation pathway; after a 1.5 h recovery period (20% O2, 5% CO2, cardiomyocyte-enriched media), cardiomyocytes treated with LAMA2-EXOs showed faster recovery than did the control group. Although EXOs had a protective effect on endothelial cells, there was no LAMA2-enhanced protection on these cells. This is the first report of LAMA2-EXOs used to treat cardiomyocytes that underwent ischemia-reoxygenation injury. Overall, we showed that membrane-specific EXOs may help improve cardiomyocyte survival in treating ischemic cardiovascular disease.

Features of Inflammatory Syndrome in Patients with COVID-19-Associated Pneumonia and Concomitant Chronic Coronary Syndrome

Introduction. The COVID-19 coronavirus disease caused by the SARS-CoV-2 virus has become an unprecedented challenge for the healthcare system and has taken a leading position among infectious diseases due to its rapid spread and development of complications in various body systems. COVID-19 has been shown to increase the long-term risk of both ischemic and nonischemic cardiovascular diseases. This underscores the need for primary prevention through measures such as vaccination and a deeper understanding of the pathophysiology linking COVID-19 to endothelial dysfunction and systemic inflammation. Patients hospitalized for coronavirus disease often have concomitant cardiometabolic disease. Cardiovascular complications are common in these patients, emphasizing the need for ongoing research to better understand these effects. The role of integral inflammatory indices in patients with coronavirus disease in the setting of chronic coronary syndromes (CCS) is unexplored.&#x0D; Aim. To identify the features of the course of chronic coronary syndromes in patients with pneumonia caused by coronavirus infection COVID-19, as well as to assess the relationship between the level of inflammatory indices and the severity of the disease.&#x0D; Materials and methods. 124 patients with COVID-19 were enrolled upon admission to the cardiology department of the Central City Clinical Hospital in Ivano-Frankivsk, the therapeutic department of the Kolomyia Central District Hospital and the therapeutic department of the Verkhovyna Hospital, 124 patients with COVID-19-associated pneumonia were selected, including 92 patients with a history of chronic coronary syndromes (CCS), including 49 patients with a history of acute myocardial infarction, 43 patients with stable angina pectoris and 32 patients without a history of CCS.&#x0D; Results of the study. The mean age of the examined patients was (66,2±7,8) years in the CCS group and (59,9±8,9) years in the non-CCS group.Among the patients with severe course, there were 36 patients (39,1%) in the CCS group and 10 patients (31,2%) in the non-CCS group. In the CCS group, 4 patients (4,3%) died, and in the non-CCS group, 2 patients (6,2%) died. The BMI in patients with CCS was (28,3 [26,2; 30,9]) kg/m2, in the group without CCS (26,66±3,59) kg/m2 and was higher in the CCS group (p=0,03). The mean number of days from the onset of symptoms to hospitalization in the CCS group was (7 [5;7] days, in the non-CCS group (7 [5;7] days). There was significant difference in the levels of inflammatory indices in the study groups after treatment, lower levels of SIRI 1,12 [0,58; 1,98] vs. 1,71 [0,74; 3,98] (p=0,04), NLR 4,22 [2,79; 5,40] vs. 5,3 [3,8; 9,56] (p=0,03), SII 936,75 [571,30; 1263,16] vs. 1198,75 [784,0; 2627,78] (p=0,008), PLR 154,75 [115,27; 208,09] vs. [124,23; 307,83] (p=0,04), AISI 253,61 [96,18; 437,47] vs.345,28 [229,48; 1040,13] (p=0,01). In the CCS group, a significant increase in the level of the LMR index (p=0,01) and a decrease in the level of CRP/L (p&lt;0,0001) were observed after treatment. According to the results of the ROC analysis, there is a significant prognostic value of the CRP/L marker for mortality in patients with COVID-19 pneumonia and concomitant CVD (AUC = 0,901; 95% CI 0,820 – 0,953; p&lt;0,0001) during hospitalization. The markers NMR, SIRI, NLR, SII, PLR, AISI, dNLR, CRP/L had a significant prognostic value for mortality when observed in the dynamics.&#x0D; Conclusions. Increased levels of inflammatory indices showed a significant value in predicting hospital mortality from COVID-19 with concomitant CCS in the dynamics but had no prognostic value during hospitalization. Patients who were discharged with recovery or improvement had lower levels of inflammatory indices in the presence of concomitant CCS in the anamnesis.

Prevention of cardiovascular disease, a major non-communicable disease, in a super-aging society: Health success and unsolved issues in Japan.

As far as non-communicable disease is concerned, Japan is unique in showing a substantial decline in stroke mortality and the lowest and declining mortality from ischemic heart disease during the past half century, which contributed to the elongation of a 4-year average life expectancy, leading to top longevity in the world. However, several issues have remained in the prevention of cardiovascular disease with super-aging: i) how to manage the screening and lifestyle modification for both individuals with metabolic syndrome and those with non-overweight/ obesity plus metabolic risk factors, and ii) how to enhance the referral of very high-risk individuals screened at health checks to physicians for seeking treatment and examine whether an early clinical visit was associated with a lower risk of cardiovascular disease and total mortality. Health counseling is needed for both persons with metabolic syndrome and high-risk individuals with non-obese/overweight because the population attributable risk fraction of ischemic cardiovascular disease was similar for both high-risk individuals. Standardized counseling for very high-risk individuals accelerated clinical visits and reduced levels of risk factors. In health counseling, public health nurses were more effective in increasing clinic visits. Furthermore, the earlier clinic visit after the counseling suggested a lower risk of hospitalization for stroke, coronary heart disease, heart failure, and all-cause mortality. This article reviews these epidemiological findings for health practitioners and policymakers to perform further prevention and control for cardiovascular disease in Japan and other Asian and African countries with emerging cardiovascular burden and aging.

Identification of a leucine-mediated threshold effect governing macrophage mTOR signalling and cardiovascular risk.

High protein intake is common in western societies and is often promoted as part of a healthy lifestyle; however, amino-acid-mediated mammalian target of rapamycin (mTOR) signalling in macrophages has been implicated in the pathogenesis of ischaemic cardiovascular disease. In a series of clinical studies on male and female participants ( NCT03946774 and NCT03994367 ) that involved graded amounts of protein ingestion together with detailed plasma amino acid analysis and human monocyte/macrophage experiments, we identify leucine as the key activator of mTOR signalling in macrophages. We describe a threshold effect of high protein intake and circulating leucine on monocytes/macrophages wherein only protein in excess of ∼25 g per meal induces mTOR activation and functional effects. By designing specific diets modified in protein and leucine content representative of the intake in the general population, we confirm this threshold effect in mouse models and find ingestion of protein in excess of ∼22% of dietary energy requirements drives atherosclerosis in male mice. These data demonstrate a mechanistic basis for the adverse impact of excessive dietary protein on cardiovascular risk.

Restoration of blood vessel regeneration in the era of combination SGLT2i and GLP-1RA therapy for diabetes and obesity.

Ischaemic cardiovascular diseases, including peripheral and coronary artery disease, myocardial infarction, and stroke, remain major comorbidities for individuals with type 2 diabetes (T2D) and obesity. During cardiometabolic chronic disease (CMCD), hyperglycaemia and excess adiposity elevate oxidative stress and promote endothelial damage, alongside an imbalance in circulating pro-vascular progenitor cells that mediate vascular repair. Individuals with CMCD demonstrate pro-vascular 'regenerative cell exhaustion' (RCE) characterized by excess pro-inflammatory granulocyte precursor mobilization into the circulation, monocyte polarization towards pro-inflammatory vs. anti-inflammatory phenotype, and decreased pro-vascular progenitor cell content, impairing the capacity for vessel repair. Remarkably, targeted treatment with the sodium-glucose cotransporter-2 inhibitor (SGLT2i) empagliflozin in subjects with T2D and coronary artery disease, and gastric bypass surgery in subjects with severe obesity, has been shown to partially reverse these RCE phenotypes. SGLT2is and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have reshaped the management of individuals with T2D and comorbid obesity. In addition to glucose-lowering action, both drug classes have been shown to induce weight loss and reduce mortality and adverse cardiovascular outcomes in landmark clinical trials. Furthermore, both drug families also act to reduce systemic oxidative stress through altered activity of overlapping oxidase and antioxidant pathways, providing a putative mechanism to augment circulating pro-vascular progenitor cell content. As SGLT2i and GLP-1RA combination therapies are emerging as a novel therapeutic opportunity for individuals with poorly controlled hyperglycaemia, potential additive effects in the reduction of oxidative stress may also enhance vascular repair and further reduce the ischaemic cardiovascular comorbidities associated with T2D and obesity.

Saponins as therapeutic candidates for atherosclerosis.

Drug development for atherosclerosis, the underlying pathological state of ischemic cardiovascular diseases, has posed a longstanding challenge. Saponins, classified as steroid or triterpenoid glycosides, have shown promising therapeutic potential in the treatment of atherosclerosis. Through an exhaustive examination of scientific literature spanning from May 2013 to May 2023, we identified 82 references evaluating 37 types of saponins in terms of their prospective impacts on atherosclerosis. These studies suggest that saponins have the potential to ameliorate atherosclerosis by regulating lipid metabolism, inhibiting inflammation, suppressing apoptosis, reducing oxidative stress, and modulating smooth muscle cell proliferation and migration, as well as regulating gut microbiota, autophagy, endothelial senescence, and angiogenesis. Notably, ginsenosides exhibit significant potential and manifest essential pharmacological attributes, including lipid-lowering, anti-inflammatory, anti-apoptotic, and anti-oxidative stress effects. This review provides a comprehensive examination of the pharmacological attributes of saponins in atherosclerosis, with particular emphasis on their role in the regulation of lipid metabolism regulation and anti-inflammatory effects. Thus, saponins may warrant further investigation as a potential therapy for atherosclerosis. However, due to various reasons such as low oral bioavailability, the clinical application of saponins in the treatment of atherosclerosis still needs further exploration.

Effects of uric acid on ischemic diseases, stratified by lipid levels: a drug-target, nonlinear Mendelian randomization study

Although uric acid-lowering agents such as xanthine oxidase inhibitors have potential cardioprotective effects, studies on their use in preventing cardiovascular diseases are lacking. We investigated the genetically proxied effects of reducing uric acid on ischemic cardiovascular diseases in a lipid-level-stratified population. We performed drug-target Mendelian randomization (MR) analyses using UK Biobank data to select genetic instruments within a uric acid-lowering gene, xanthine dehydrogenase (XDH), and construct genetic scores. For nonlinear MR analyses, individuals were stratified by lipid level. Outcomes included acute myocardial infarction (AMI), ischemic heart disease, cerebral infarction, transient cerebral ischemic attack, overall ischemic disease, and gout. We included 474,983 non-gout individuals with XDH-associated single-nucleotide polymorphisms. The XDH-variant-induced uric acid reduction was associated with reduced risk of gout (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.78–0.93; P < 0.001), cerebral infarction (OR, 0.86; 95% CI, 0.75–0.98; P = 0.023), AMI (OR, 0.79; 95% CI, 0.66–0.94; P = 0.010) in individuals with triglycerides ≥ 188.00 mg/dL, and cerebral infarction in individuals with low-density lipoprotein cholesterol (LDL-C) ≤ 112.30 mg/dL (OR, 0.76; 95% CI, 0.61–0.96; P = 0.020) or LDL-C of 136.90–157.40 mg/dL (OR, 0.67; 95% CI, 0.49–0.92; P = 0.012). XDH-variant-induced uric acid reduction lowers the risk of gout, AMI for individuals with high triglycerides, and cerebral infarction except for individuals with high LDL-C, highlighting the potential heterogeneity in the protective effects of xanthine oxidase inhibitors for treating AMI and cerebral infarction depending on the lipid profiles.

Mechanism analysis of Buyang Huanwu decoction in treating atherosclerosis based on network pharmacology and invitro experiments.

Atherosclerosis (AS) is one of the main risk factors of ischemic cardiovascular and cerebrovascular diseases. Buyang Huanwu decoction (BYHWT) is a classic Chinese medicine prescription that is used for treating AS. However, the underlying pharmacological mechanism remains unclear. This study aims to clarify the molecular mechanism of BYHWT in treatment of AS through network pharmacology and invitro experiments. Molecular structure information and targets of core components of BYHWT were obtained from PubChem and UniProtKB databases. Genes involved in AS were obtained from DisGeNet, GeneCards and OMIM databases. The core targets of BYHWT in AS treatment were identified by protein-protein interaction (PPI) network analysis with STRING platform, and analyzed by gene ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomics (KEGG) pathway enrichment analysis. Molecular docking was used to verify the binding affinity between the core targets and the bioactive ingredients. HUVEC viability, inflammatory response and mRNA expression levels of core target genes were evaluated by cell counting kit 8 assay, enzyme-linked immunosorbent assay (ELISA) and qRT-PCR. A total of 60 candidate compounds and 325 predicted target genes were screened. PPI network analysis suggested that TP53, SRC, STAT3, and AKT1 may be the core targets. BYHWT in AS treatment was associated with 46 signaling pathways. GA120, baicalein, and 3,9-di-o-methylnissolin had good binding affinity with core target proteins. Baicalein treatment could significantly promoted the viability and repress the inflammatory response of HUVEC cells stimulated by ox-LDL. In addition, Baicalein can regulate the expression of core targets including AKT1, MAPK1, PIK3CA, JUN, TP53, SRC, EGFR, and ESR1. In conclusion, BYHWT and its main bioactive component baicalein, inhibit inflammatory response and modulate multiple downstream genes of endothelial cells, and show good potential to block the progression of AS and cardiovascular/cerebrovascular diseases.

Pop-Out Myocardial Infarction Induction in Mice.

Myocardial infarction (MI) in mice is a widely used surgical model in preclinical cardiac repair studies to recapitulate human cardiovascular ischemic disease. Induction of reproducible infarct size is crucial for quantitative and analytical purpose. Here we describe a quick and reliable method to induce consistent infarct size in mice in less than a minute.

A Luciferase Reporter Assay to Detect Cellular Hypoxia In Vitro.

Hypoxia is a hallmark of ischemic cardiovascular diseases and solid malignant tumors. Cellular hypoxia induces numerous physiological and pathological processes, including hematopoiesis, angiogenesis, metabolic changes, cell growth, and apoptosis. Hypoxia-inducible factor-1 (HIF-1) binds to hypoxia response elements (HREs) to selectively induce the expression of various genes in response to hypoxia. Therefore, HREs have been used to develop hypoxia-targeted gene therapy.More than 70 pairs of HREs and hypoxia-inducible genes have been identified. The hypoxia-induced gene expression levels vary among HRE sequences depending on the number of HRE copies and oxygen levels. Most known HREs have not yet been thoroughly studied. Recent studies have revealed that the HRE-mediated effects of hypoxia are cell line-dependent. Herein we describe an in vitro method to investigate gene activation levels and characteristics based on varying the copy number of HREs in response to cellular hypoxia. We explain how to clone HREs into luciferase reporter constructs in the sense, antisense, and dual directions to measure luciferase expression for functional analyses.