Antiatherogenic Properties Research Articles

Peptides as Therapeutic Agents for Atherosclerosis.

More than three decades ago, as a test for the amphipathic helix theory, an 18 amino acid residue peptide and its analogs were designed with no sequence homology to any of the exchangeable apolipoproteins. Based on the apolipoprotein A-I (the major protein component of high density lipoproteins, HDL) mimicking properties, they were termed as ApoA-I mimicking peptides. Several laboratories around the world started studying such de novo-designed peptides for their antiatherogenic properties. The present chapter describes the efforts in bringing these peptides as therapeutic agents for atherosclerosis and several lipid-mediated disorders.

Antioxidant, anti-proliferative, and anti-atherosclerotic effect of phytochemicals isolated from Trachyspermum ammi with honey in RAW 264.7 and THP-1 cells

Background: Trachyspermum ammi is a common spice with vital medicinal properties used in Ayurveda to treat many ailments. Furthermore, natural Honey is said to have high levels of antioxidants and anti-inflammatory properties. While the combination of both T. ammi and Honey is unexplored in anti-atherosclerotic activity. Materials and Methods: Assays guided isolation of carotenoids, phenolics, and tannins were performed by methanol and aqueous extraction from T. ammi seed powder and honey mixture. Phytochemical screening for antioxidant activity (superoxide radical scavenging activity, nitric oxide radical scavenging activity, and 2, 2-diphenyl-1-picrylhydrazyl scavenging activity) and antilipidemic activity by inhibition of low-density lipoprotein (LDL) oxidation were investigated. Sample showing highest activity with lowest IC50 value from antioxidant and antilipidemic activity was further evaluated on RAW 264.7, THP-1 cells for foam cell inhibition activity, anti-proliferation, antiapoptotic activity, and nitric oxide assay. The sample was characterized using high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS). Results: Out of the phytochemicals screened, tannin methanol extract (TME) showed the highest antioxidant activity with IC50 value having 7.11 μg/mL in superoxide scavenging assay, the IC50 value of 1.46 μg/mL by nitric oxide scavenging assay, and followed by IC50 value of 20.83 μg/mL in 2, 2-diphenyl-1-picrylhydrazyl activity. The results showed that it also efficiently inhibited LDL oxidation at 240 μg/mL (71.29% at 5 h)., thus inhibiting foam cell development, preventing proliferation, apoptosis, and nitrate production in cultured RAW 264.7 and THP-1 cells. HPLC analysis showed the presence of tannin in the extract. TME was characterized in GC-MS, which showed 13 prominent compounds. Conclusion: The scientific evidence in the present study showed that the TME from T. ammi seed powder and honey act as an antioxidant and antiatherogenic properties in inhibiting foam cell formation. Hence, this phytochemical can be used for the treatment of atherosclerosis.

Preparation of LDL , Oxidation , Methods of Detection, and Applications in Atherosclerosis Research.

The concept of lipid peroxidation has been known for a long time. It is now well established that LDL plays a major role in atherosclerosis. Oxidized low-density lipoprotein (Ox-LDL) has been studied for over 35years. Numerous pro- and anti-atherogenic properties have been attributed to Ox-LDL. Component composition of Ox-LDL is complex due to the influence of various factors, including the source, method of preparation, storage and use. Hence, it is very difficult to clearly define and characterize Ox-LDL. It contains unoxidized and oxidized fatty acid derivatives both in the ester and free forms, their decomposition products, cholesterol and its oxidized products, proteins with oxidized amino acids and cross-links, polypeptides with varying extents of covalent modification with lipid oxidation products and many others. The measurement of lipid oxidation has been a great boon, not only to the understanding of the process but also in providing numerous serendipitous discoveries and methodologies. In this chapter, we outline the methodologies for the preparation and testing of various lipoproteins for oxidation studies.

Detection of adulteration in market ghee using FT-IR Spectroscopy

Abstract: Dairy ghee is a prominent synergistic fat product that is comprised of various health benefiting compounds such as milk fat globule membrane, conjugated linoleic acid, and short-chain free fatty acids. It emanates numerous beneficial actions on human heath are anticancer, antidiabetic, anticholesterolemic, antimicrobial, antioxidant, antiatherogenic and anitadipogenic properties. In order to increase the quantity for marketing purposes, ghee is adulterated with low quality fats. These adulterated low quality fats have long-chain fatty acids and trans-fats which causes cardiac diseases, obesity and renal dysfunction. Hence, the present study aimed to detect the adulterant in ghee by Fourier transform infrared spectroscopy method. It also shows the quantitative increase of adulterated animal body fat with ghee. The peak C=C increases with the raise of alkene concentration. The N-H bend peak, which represents amines, determines the trans-fat adulteration, causes health-related issues. Thus, FT-IR technique proved the ideal tools for detecting and estimating the degree of ghee adulteration. Keywords: FT-IR, Ghee, Adulteration, Commercial brands, Beef fat.

Evaluation of the Vasoprotective Effects of Metformin versus Glibenclamide in Type 2 Diabetic Patients

Adiponectin (APN) is an adipokine with anti-inflammatory and anti-atherogenic properties decreased in type 2 diabetes mellitus (T2DM) that may influence endothelial function by regulating serum nitric oxide (NO) levels. The current study aimed to investigate the effect of two oral hypoglycemic drugs, Metformin and Glibenclamide (GLC), on circulating APN and NO levels and to find a correlation between APN and NO levels in type 2 diabetic patients. Fifty males and females previously diagnosed with T2DM were conducted in this trial and classified into groups: Group A involved 18 untreated patients with T2DM, group B involved 16 patients receiving Metformin monotherapy (1000 mg/day) for up to 1 year and group C involved 16 patients receiving GLC (5 mg/day) for up to 1 year. Circulating APN and NO were measured. Compared to GLC, Metformin therapy showed a significant increase in APN and NO levels in type 2 diabetic patients. Our findings established that Metformin has a protective effect on endothelial function, including increased APN and NO bioavailability, beyond its glucose-lowering effect.

The Effective Role of Natural Product Berberine in Modulating Oxidative Stress and Inflammation Related Atherosclerosis: Novel Insights Into the Gut-Heart Axis Evidenced by Genetic Sequencing Analysis.

The exacerbation of oxidative and inflammatory reactions has been involved in atherosclerotic cardiovascular diseases leading to morbidity and mortality worldwide. Discovering the underlying mechanisms and finding optimized curative approaches to control the global prevalence of cardiovascular diseases is needed. Growing evidence has demonstrated that gut microbiota is associated with the development of atherosclerosis, while berberine, a natural product exhibits antiatherogenic effects in clinical and pre-clinical studies, which implies a potential link between berberine and gut microbiota. In light of these novel discoveries, evidence of the role of berberine in modulating atherosclerosis with a specific focus on its interaction with gut microbiota is collected. This review synthesizes and summarizes antioxidant and anti-inflammatory effects of berberine on combating atherosclerosis experimentally and clinically, explores the interaction between berberine and intestinal microbiota comprehensively, and provides novel insights of berberine in managing atherosclerotic cardiovascular diseases via targeting the gut-heart axis mechanistically. The phenomenon of how berberine overcomes its weakness of poor bioavailability to conduct its antiatherogenic properties is also discussed and interpreted in this article. An in-depth understanding of this emerging area may contribute to identifying therapeutic potentials of medicinal plant and natural product derived pharmaceuticals for the prevention and treatment of atherosclerotic cardiovascular diseases in the future.

Treatment of Cardiovascular Disease in Rheumatoid Arthritis: A Complex Challenge with Increased Atherosclerotic Risk.

Rheumatoid arthritis (RA) carries significant risk for atherosclerotic cardiovascular disease (ASCVD). Traditional ASCVD risk factors fail to account for this accelerated atherosclerosis. Shared inflammatory pathways are fundamental in the pathogenesis of both diseases. Considering the impact of RA in increasing cardiovascular morbidity and mortality, the characterization of therapies encompassing both RA and ASCVD management merit high priority. Despite little progress, several drugs discussed here promote remission and or lower rheumatoid disease activity while simultaneously conferring some level of atheroprotection. Methotrexate, a widely used disease-modifying drug used in RA, is associated with significant reduction in cardiovascular adverse events. MTX promotes cholesterol efflux from macrophages, upregulates free radical scavenging and improves endothelial function. Likewise, the sulfonamide drug sulfasalazine positively impacts the lipid profile by increasing HDL-C, and its use in RA has been correlated with reduced risk of myocardial infraction. In the biologic class, inhibitors of TNF-α and IL-6 contribute to improvements in endothelial function and promote anti-atherogenic properties of HDL-C, respectively. The immunosuppressant hydroxychloroquine positively affects insulin sensitization and the lipid profile. While no individual therapy has elicited optimal atheroprotection, further investigation of combination therapies are ongoing.

51 Palmitoylethanolamide associated to polydatin reduces inflammation in human endothelial vascular cells exposed to doxorubicin and trastuzumab through PPAR-a and NLRP3-related pathways

Abstract Aims Palmitoylethanolamide is an endogenous fatty acid mediator that is synthetized from membrane phospholipids by N-acyl phosphatidylethanolamine phospholipase D. Polydatin is a nutraceutical agent derived from trans-resveratrol with established anti-inflammatory and anti-atherogenic properties. We aimed to assess whether palmitoylethanolamide combined to polydatin, co-incubated during doxorubicin and trastuzumab, reduces anticancer drugs-related cardiotoxicity in cellular models. Methods Human vascular endothelial cells were exposed to subclinical concentration of doxorubicin (at 100 and 200 nM) combined to trastuzumab (at 100 and 200 nM) alone or in combination with a formulation composed by palmitoylethanolamide and polydatin (500 nM and 50 µM, respectively) for 48 h. After the incubation period, we performed the following tests: determination of cell viability, through analysis of mitochondrial dehydrogenase activity, study of lipid peroxidation (quantifying cellular Malondialdehyde and 4-hydroxynonenal), intracellular Ca2+ homeostasis. Moreover, pro-inflammatory studied were also performed (activation of NLRP3 inflammasome; expression of peroxisome proliferator-activated receptor-α; mTORC1 Fox01/3a; transcriptional activation of p65/NF-κB and secretion of cytokines involved in cardiotoxicity (Interleukins 1β, 8, 6). Results Palmitoylethanolamide combined to polydatin co-incubated with doxorubicin exerts vasculoprotective effects, enhancing cell viability of 54.7–68.3% compared to untreated cells (P < 0.001 for all). The formulation reduced significantly the cardiotoxicity through peroxisome proliferator-activated receptor-α–related pathways and NLRP3 inflammasome but without the involvement of calcium homeostasis. Conclusion The present study demonstrates that palmitoylethanolamide and polydatin protects against vasculotoxicity of doxorubicin and trastuzumab by promoting an anti-inflammatory phenotype, representing a new therapeutic approach to resolve doxorubicin-induced vasculotoxicity and inflammation.

The Gastroprotective Effect of Naringenin against Ethanol-Induced Gastric Ulcers in Mice through Inhibiting Oxidative and Inflammatory Responses.

Naringenin is a major flavanone found in grapes, tangelos, blood oranges, lemons, pummelo, and tangerines. It is known to have anti-inflammatory, antioxidant, anticancer, antimutagenic, antifibrogenic, and antiatherogenic pharmacological properties. This study aims to investigate the anti-inflammatory effects of naringenin in ethanol-induced gastric damage in vivo and ethanol-stimulated KATO III cells in vitro. Our results showed that pretreatment with naringenin significantly protected mice from ethanol-induced hemorrhagic damage, epithelial cell loss, and edema with leucocytes. It reduced gastric ulcers (GU) by suppressing ethanol-induced nuclear factor-κB (NF-κB) activity and decreasing the levels of nitric oxide (NO), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), and myeloperoxidase (MPO). In addition, pretreatment with naringenin might inhibit the secretion of TNF-α, IL-6, and IL-8, as well as the proteins cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) via the suppression of NF-κB and mitogen-activated protein kinase (MAPK) signaling in ethanol-stimulated stomach epithelial KATO III cells. Together, the results of this study highlight the gastroprotective effect of naringenin in GU of mice by inhibiting gastric secretion and acidity, reducing inflammation and oxidative stress, suppressing NF-κB activity, and restoring the histological architecture. These findings suggested that naringenin has therapeutic potential in the alleviation of ethanol-induced GU.

Association between Paraoxonase-1 p.Q192R Polymorphism and Coronary Artery Disease susceptibility in the Colombian Population.

BackgroundParaoxonase-1 (PON1), a glycoprotein associated with serum high-density lipoprotein (HDL), has a central role in metabolizing lipid peroxides, exhibiting antiatherogenic properties. The polymorphism p.Q192R has been previously associated with coronary artery disease (CAD) susceptibility and clopidogrel response.PurposeWe aimed at investigating the association of PON1 p.Q192R with CAD and clopidogrel response in Colombian population.Patients and MethodsThe study was conducted among 163 patients diagnosed with CAD and treated with clopidogrel. The allele frequencies for the PON1 192Q and 192R alleles were determined in cases and Latin-American controls obtained from the public database gnomAD (n = 17,711). Response to clopidogrel was determined by assessing the platelet function using the INNOVANCE PFA-200 System. We determined the association between PON1 p.Q192R polymorphism, increased susceptibility to CAD and high on-treatment platelet reactivity (HPR) by using odds ratio (OR) and 95% confidence interval (CI) on four genetic models.ResultsThe allele frequencies for the PON1 192Q and 192R alleles were 0.60 and 0.40, respectively. The allele distribution was found to be statistically different from the control group and other ethnic groups. The allele 192R was positively associated with decreased susceptibility to CAD under a dominant model (OR, 0.58; 95% CI, 0.42–0.8; P < 0.01). We found no association between the polymorphism and HPR.ConclusionWe propose that PON1 p.Q192R is a potentially useful marker for CAD susceptibility in the Colombian population and lacks association with HPR under clopidogrel treatment.

RELATIONSHIP BETWEEN ADIPONECTIN AND MYOCARDIAL INFARCTION AMONG DIABETIC PATIENTS

Adiponectin (AD) is an adipocyte-specific secretory protein that is highly expressed in adipose tissue. AD levels are decreased in patients with cardiovascular diseases and type 2 diabetes (DM). This study aimed to analyze the relationship between low levels of adiponectin, diabetes and myocardial infarction. A systematic review was conducted following the PRISMA guidelines. Papers were selected searching PubMed/Medline database in July 2021 using the terms [adiponectin] AND [diabetes] AND [myocardial infarction]. The inclusion criteria were limited to observational studies that evaluated the association between adiponectin index in myocardial infarction among diabetic patients. There were no language or publication date restrictions.Among the 130 papers initially identified, 49 were eligible for this review. AD, inhibits liver gluconeogenesis, displays anti-atherogenic and anti-inflammatory properties and promotes peripheral insulin sensitivity. Lower levels of AD are related to a higher risk of myocardial infarction and a worse prognosis in patients with coronary artery disease. Favorable effects of AD are associated with maintained ischemia-induced angiogenesis, decreased myocyte death, decreased hypertrophic response, reduced interstitial fibrosis and attenuated inflammatory response. It has been suggested that high molecular weight AD is more important for vascular protection. Nevertheless, it is unknown if higher levels of AD are associated with a reduced risk for coronary heart disease and myocardial infarction among diabetic individuals.Although the adiponectin´s pattern of cardioprotection is well stablished, it is still unclear if higher levels are associated with reduced risk of coronary heart disease and myocardial infarction among diabetic individuals.

THE LEVEL OF SERUM ADIPONECTIN AND ITS POSSIBLE ROLE IN RHEUMATOID ARTHRITIS PATIENTS

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease that damages joints and impairs daily life for those affected. RA is caused on by three risk factors: genetics, gender, and smoking. Factors such as pro-inflammatory chemicals, insulin resistance, total oxidant status, adhesion molecules and the use of corticosteroids in chronic inflammatory disorders also contribute to the acceleration of atherosclerosis. Adipose tissue plays an important role in maintaining overall body balance. There are numerous bioactive peptides known as adipo(cyto)kines secreted by adipocytes. Adiponectin, the most common adipokine produced by adipose tissue, has anti-atherogenic properties. Adiponectin has 244 amino acids and is an abundant protein hormone. Recent study suggests that adiponectin may be useful in the diagnosis of RA and other rheumatic diseases.

Correlation between HDL2, HDL3 and serum ferritin levels with fatty liver and NAFLD activity score (NAS) in liver histology of organ donors

BackgroundNonalcoholic fatty liver disease (NAFLD) is one of the most important liver diseases. High-density lipoprotein (HDL) has anti-atherogenic properties and its reduction can be associated with fatty liver. Serum ferritin levels are usually elevated in patients with NAFLD. This study aimed to evaluate the correlation between HDL subtypes and serum ferritin levels with evidence of NAFLD in liver histology of organ donors.Methods One hundred organ donor patients who were eligible for the study were included in the study and ferritin; HDL2 and HDL3 were measured in blood samples. Donated liver tissue biopsy specimens were evaluated for fatty liver and NAFLD activity score (NAS). In addition, AST and ALT were measured in recipients 24 h after transplant. All data abstracted and analyzed statistically.ResultsSerum HDL2 levels and HDL2/HDL3 ratio in patients with NAS > 1 were significantly lower (P < 0.05). Serum levels of HDL3 and ferritin were not significantly associated with NAS >1 (P > 0.05). In addition, serum ferritin > 1000 ng/ml in organ donors associated with increased AST and ALT levels 24 h after transplantation in the liver organ recipient.ConclusionsLower HDL2 values and HDL2/HDL3 ratio were associated with increased NAFLD activity score, but HDL3 and ferritin did not show such a relationship. In addition, higher levels of ferritin in organ donors may be associated with increased AST and ALT 24 h after liver transplantation in the organ recipient.

Therapeutic Potential of Mitophagy-Inducing Microflora Metabolite, Urolithin A for Alzheimer's Disease.

Mitochondrial dysfunction including deficits of mitophagy is seen in aging and neurodegenerative disorders including Alzheimer’s disease (AD). Apart from traditionally targeting amyloid beta (Aβ), the main culprit in AD brains, other approaches include investigating impaired mitochondrial pathways for potential therapeutic benefits against AD. Thus, a future therapy for AD may focus on novel candidates that enhance optimal mitochondrial integrity and turnover. Bioactive food components, known as nutraceuticals, may serve as such agents to combat AD. Urolithin A is an intestinal microbe-derived metabolite of a class of polyphenols, ellagitannins (ETs). Urolithin A is known to exert many health benefits. Its antioxidant, anti-inflammatory, anti-atherogenic, anti-Aβ, and pro-mitophagy properties are increasingly recognized. However, the underlying mechanisms of urolithin A in inducing mitophagy is poorly understood. This review discusses the mitophagy deficits in AD and examines potential molecular mechanisms of its activation. Moreover, the current knowledge of urolithin A is discussed, focusing on its neuroprotective properties and its potential to induce mitophagy. Specifically, this review proposes potential mechanisms by which urolithin A may activate and promote mitophagy.

Adiponectin: a pleiotropic hormone with multifaceted roles.

Adipose tissue mostly composed of different types of fat is one of the largest endocrine organs in the body playing multiple intricate roles including but not limited to energy storage, metabolic homeostasis, generation of heat, participation in immune functions and secretion of a number of biologically active factors known as adipokines. The most abundant of them is adiponectin. This adipocite-derived hormone exerts pleiotropic actions and exhibits insulin-sensitizing, antidiabetic, anti-obesogenic, anti-inflammatory, antiatherogenic, cardio- and neuroprotective properties. Contrariwise to its protective effects against various pathological events in different cell types, adiponectin may have links to several systemic diseases and malignances. Reduction in adiponectin levels has an implication in COVID-19-associated respiratory failure, which is attributed mainly to a phenomenon called 'adiponectin paradox'. Ample evidence about multiple functions of adiponectin in the body was obtained from animal, mostly rodent studies. Our succinct review is entirely about multifaceted roles of adiponectin and mechanisms of its action in different physiological and pathological states.

Nutraceutical and Therapeutic Properties of Edible Super Food: Pumpkin Seeds - A Review

Pumpkin seeds, despite their small size, are loaded with enough nutrients necessary to protect the human body against various health issues. Pumpkin seeds, also called as “Pepita” can be incorporated easily into the diet. They are good sources of minerals like magnesium, zinc and amino acid tryptophan, which helps to promote good sleep. They also have high tocopherol content, which makes them a rich source of antioxidants. Phytochemical screening indicated the presence of alkaloids, flavonoids, steroids, diterpenes, saponins, and phenols. High dietary fiber content in these seeds help reduce the risk of heart disease, high blood pressure (hypertension), type 2 diabetes and obesity. Gas chromatographic analysis of the pumpkin seed oil (PSO) showed that the linoleic (39.84%), oleic (38.42%), palmitic (10.68%) and stearic (8.67%) acids were the major fatty acids present in PSO. Studies revealed that PSO can be a valuable source of edible oil due to their high poly unsaturated fatty acids (PUFA) content when compared to other vegetable oils. Besides this, bioactive compounds from the pumpkin seeds are known for their anthelmintic, antidiabetic, antidepressant, antioxidant, anti-atherogenic, hypolipidemic, immunomodulator, antitumor, and cytoprotective properties. United States Pharmacopoeia had included pumpkin seeds as an official medicine for parasite elimination from 1863 to 1936. Literature studies revealed that pumpkin seeds can be used as a traditional and functional food ingredient provided further animal and clinical investigations are carried out to establish the respective molecular mechanisms. The present paper reviews about the nutraceutical and therapeutic applications of this super food.

The Promise of Apolipoprotein AI-Based Therapy

Apolipoprotein A-I (ApoAI) is an anti-atherosclerotic protein that promotes cholesterol efflux from tissues to the liver for excretion [1]. ApoAI is the main structural and functional protein of High- Density Lipoproteins (HDL), representing ~70% of total HDL proteins [2,3]. Circulating apoAI protein is an amphipathic protein (28kDa) comprising eight alpha-helical domains of 22 amino acids and two repeats of 11 amino acids [4]. Consequently, ApoAI binds avidly to lipids and readily moves between lipoprotein particles; however, ~5-10% of human plasma ApoAI exists in a free state (lipoprotein-unbound) [5]. ApoAI protein is more than a structural scaffold that maintains lipid packaging, as it plays an important role in the transport of cellular cholesterol from the artery wall to the liver for catabolism [6-8]. Antioxidant and anti-inflammatory properties were also attributed to apoAI [9,10]. In addition, a protective role of apoAI against cancer was proposed [11]. ApoAI is synthesized mainly in the liver and small intestine and there are a lot of regulatory elements and transcription factors that control apoAI gene expression, as reviewed in [12]. Treatment with BPA (bisphenol A), one of the most widespread environmental chemicals, downregulates ApoAI gene expression, aggravating the atherosclerotic plaques in LDLR-/- mice [13]. Interestingly, the ratio of HDL-cholesterol to apoAI protein levels is an indicator of the risk of the cardiovascular disorder [14]. Lack of ApoAI augmented atherosclerosis in various hypercholesterolemic mice, such as mice expressing human apoB or ApoAI-/-/LDLR-/- mice [15,16]. In humans, familial ApoAI deficiency is associated with premature coronary heart disease [17]. Interestingly, low levels of apoAI and atherogenic dyslipidemia were found in obese individuals, but increases in apoAI levels and enhancements of cholesterol efflux capacity of HDL were reported at three months after bariatric surgery [18]. Considering the anti-atherogenic properties of apoAI, various apoAI-based therapies were proposed for reduction of atherogenesis: i) overexpression of ApoAI, ii) infusions of ApoAI protein, ApoAI mimetic peptides, or ApoAI-containing HDL [19-21], iii) oral small molecules that stimulate ApoAI production [22]. Overexpression of ApoAI reduced atherogenesis in apoE-/- or LDLR-/- atherosclerotic mice [23-31]. Infusions of ApoAI mimetic peptides led to the regression of aortic valve stenosis in rabbits [32]. Liver-directed adenoviral gene transfer of ApoAI resulted in the regression of preexisting atheroma in LDLR-/- mice [33]. Undoubtedly, local delivery of apoAI protein to the vascular wall represents a more efficient apoAIbased therapy than its systemic delivery. Remarkably, transduction of vascular endothelial cells with ApoAI expressing adenovirus reduced inflammation and protected against atherosclerosis in hyperlipidemic rabbits [34,35]. The oral drug RVX-208 significantly increased apoAI production in monkeys but presented disappointing efficacy in a phase II trial [36]. Notwithstanding there are good results obtained in studies using animal models, several apoAI-based clinical trials failed to regress atherosclerotic plaques in humans [37,38]. Despite tremendous advances regarding the understanding of apoAI, the promise of apoAI-based therapy awaits new studies and trials.

Very low high-density lipoprotein-cholesterol and long-term mortality

Abstract Background High-density lipoprotein-cholesterol (HDL-C) has anti-atherogenic, anti-inflammatory, anti-oxidative, anti-apoptotic, and vasodilatory properties. While a linear inverse relationship between HDL-C levels and all-cause mortality is established, recent observational studies suggest a U-shaped association between HDL-C and outcome. Purpose We tested the hypothesis that both low and high HDL-C levels associate with long-term mortality. Methods The present analysis is based on the longitudinal ECAD registry of consecutive patients undergoing coronary angiography at the West German Heart and Vascular Center between 2004 and 2019. HDL-C was quantified at hospital admission using standardized enzymatic methods. The incidence of death due to any cause was evaluated during follow-up. Cox regression analysis was used to determine the association of HDL-C with incident mortality, adjusting for age, sex, systolic blood pressure, low-density lipoprotein cholesterol, smoking status, and family history of premature cardiovascular disease. In addition to the analysis on HDL-C as continuous variable, the association of HDL-groups (&amp;lt;10th percentile, 10th-&amp;lt;25th percentile, 25th-&amp;lt;50th percentile, 50th-&amp;lt;75th percentile, 75th-90th percentile, and ≥90thpercentile) with incident mortality was determined using HDL-C &amp;lt;10th percentile as reference. Results Among 17,433 patients, mean age was 65.9±12.6 years and 70.1% were men. Mean HDL-C was 48.7±16.2 mg/dL. During a mean follow-up 3.38±2.10 years, 2,401 patients (13.8%) died. In multivariable analysis, higher HDL-C levels were independently associated with lower all-cause mortality [hazard ratio (95% confidence interval): 0.83 (0.76, 0.91) per 1 standard deviation change in HDL-C, p&amp;lt;0.001]. Associations between HDL-C and mortality were equally present in male [0.83 (0,74, 0.93), p=0.001] and female patients [0.85 (0.73, 1.00), p=0.0496]. Using HDL-C &amp;lt;10thpercentile as reference (&amp;lt;31mg/dl), all other HDL-C groups showed stable effect sizes below 1.0 without signs of increasing morality probability in high HDL-C groups [0.50 (0.44, 0.58), p&amp;lt;0.001; 0.41 (0.36, 0.46), p&amp;lt;0.001; 0.37 (0.32, 0.42), p&amp;lt;0.001; 0.36 (0.36, 0.31), p&amp;lt;0.001; and 0.40 (0.34, 0.47), p&amp;lt;0.001 for HDL-C 31–37 mg/dL, 38–45 mg/dL, 46–56 mg/dL, 57–69 mg/dL, and ≥70mg/dl, respectively]. Conclusions In a large longitudinal registry cohort of patients undergoing invasive coronary angiography, only very low HDL-C levels were associated with increased long-term mortality. We found no signs of a U-shaped association between HDL-C and prognosis. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Iryna Dykun was supported by the German Research Foundation (DY 149/2-1)Stefanie Hendricks was supported by the Universitätsmedizin Essen Clinician Scientist Academy (UMEA)

The relationship between high-density lipoprotein cholesterol (HDL-C) and glycosylated hemoglobin in diabetic patients aged 20 or above: a cross-sectional study

AimThe incidence rate of diabetes is increasing year by year, seriously threatening human health. As a predictor of glycemic control, glycated hemoglobin is reported to be related to various complications and prognoses of diabetes. Besides, HDL-C dyslipidemia is a component of metabolic syndrome and may be related to various cardiovascular and cerebrovascular diseases. The principal objective of this project was to investigate the relationship between HDL-C and glycosylated hemoglobin in adult diabetic patients.MethodsA total of 3171 adult diabetic patients aged 20 years and above were included in the present study from the National Health and Nutrition Examination Survey (NHANES). HDL-C and glycosylated hemoglobin were regarded as independent and dependent variables, respectively. EmpowerStats software and R (version 3.4.3) were used to examine the association between HDL-C and glycosylated hemoglobin.ResultsHDL-C was inversely associated with glycohemoglobin after adjusting for other covariates (β = − 0.004, 95% CI:− 0.008 to − 0.000, p = 0.044). Race/ethnicity and age were considered the most prominent interactive factors that affect the relationship between HDL and glycosylated hemoglobin by the interaction analysis. A U-shaped association was detected between HDL-C and glycosylated hemoglobin for people of other race/ethnicity or aged 60 and above, which had an inflection point of HDL-C at 60 mg/dL. In contrast, we observed an inverted U-shaped distribution between HDL-C and glycosylated hemoglobin in people under 40 with point of inflection located at 60 mg/dL as well.ConclusionsHDL-C in diabetic patients is inversely associated with glycosylated hemoglobin and may be relevant to glycemic control. However, a U-shaped relationship was also observed in a certain kind of people, which implied that, though HDL-C is considered as metabolism and anti-atherogenic property, for diabetics, it is not the higher, the better.

Study of Some Inflammatory Mediators in the Serum of Patients With Atherosclerosis and Acute Myocardial Infarction.

Background and aim of the studyThe aim of this study is to evaluate the changes in the inflammatory mediator’s serum amyloid A (SAA), adiponectin, and resistin in the serum of patients with stable angina and acute myocardial infarction.Subjects and methodsThe study was done on 60 subjects divided into three groups: 20 healthy normal individuals as a control group, 20 patients with stable angina (atherosclerotic plaque), and 20 patients with myocardial infarction. Fasting blood samples were withdrawn from all subjects and serum was prepared. SAA, resistin, and adiponectin levels were quantitatively measured by enzyme-linked immunosorbent assay (ELISA).ResultsThe SAA level was significantly higher in both stable angina and the acute myocardial infarction group than the control group (2.7179 ± 0.44501 mg/L) and the serum resistin level was significantly higher (p-value = 0.0) in the stable angina (8.368 ± 1.633 ng/ml) and the acute myocardial infarction (13.606 ± 2.067 ng/ml) groups (p-value= 0.0) than the control group. (2.4272±1.25210 ng/ml). Moreover, resistin levels in stable angina when compared to the AMI showed a significant difference between them (p-value = 0.0) while adiponectin was significantly lower in the acute myocardial infarction group. (6.641±2.6011 µg/mL, p-value = 0.019) than its level in the control group (11.873±1.798 µg/mL). While the adiponectin level showed no significant differences between stable angina in comparison to the AMI.ConclusionSAA can be used as a confirmatory marker for stable angina and a diagnostic tool for AMI patients. Both SAA and resistin may participate in the atherosclerosis process as an effectors molecule of inflammatory reactions. For adiponectin, we concluded that it has the antiatherogenic property and its levels were lower in both the stable angina and acute myocardial infarction groups.