Prevention Of Atherosclerosis Research Articles

Capsaicin Improves Systemic Inflammation, Atherosclerosis, and Macrophage-Derived Foam Cells by Stimulating PPAR Gamma and TRPV1 Receptors

Background: Capsaicin, a bioactive compound found in peppers, is recognized for its anti-inflammatory, antioxidant, and anti-lipidemic properties. This study aimed to evaluate the effects of capsaicin on atherosclerosis progression. Methods: Apolipoprotein E knockout mice and their C57BL/6 controls were utilized to assess blood lipid profile, inflammatory status, and atherosclerotic lesions. We also examined the influence of capsaicin on cholesterol influx and efflux, and the role of TRPV1 and PPARγ signaling pathways in bone marrow-derived macrophages. Results: Capsaicin treatment reduced weight gain, visceral adiposity, blood triglycerides, and total and non-HDL cholesterol. These improvements were associated with a reduction in atherosclerotic lesions in the aorta and carotid. Capsaicin also improved hepatic oxidative and inflammatory status. Systemic inflammation was also reduced, as indicated by reduced leukocyte rolling and adhesion on the mesenteric plexus. Capsaicin decreased foam cell formation by reducing cholesterol influx through scavenger receptor A and increasing cholesterol efflux via ATP-binding cassette transporter A1, an effect primarily linked to TRPV1 activation. Conclusions: These findings underscore the potential of capsaicin as a promising agent for atherosclerosis prevention, highlighting its comprehensive role in modulating lipid metabolism, foam cell formation, and inflammatory responses.

Whole Food Plant-Based Dietary Education for Frontline RNs

Background: Coronary artery disease (CAD) is the leading cause of death for men and women in the United States, with myocardial infarction (MI) being a serious outcome. Plant-based diets are associated with a reduced incidence of CAD. Registered nurses (RNs) are highly trusted members of the healthcare team and are ethically responsible for providing reliable information based on scientific sources and guideline-directed recommendations. Registered nurses are optimally positioned to provide education on adopting whole foods plant-based (WFPB) diets to patients experiencing CAD inside and outside the hospital setting. It is unknown the degree to which nurses have adopted WFPB eating patterns and incorporated WFPB patient education into routine nursing care. The purpose of this study is to describe RN perceptions (susceptibility, severity, benefits and barriers, self-efficacy) related to the effect of a WFPB meal pattern for prevention and management of CAD, and RN intention to apply this dietary knowledge to their own health behaviors and nursing practices. Methods: This descriptive quasi-experimental pretest-posttest study measured concepts from the health belief model including RN perceptions of susceptibility, severity, benefits, and barriers, as well as self-efficacy and meal behaviors. The participating RNs completed these measures before and after they participated in any of the educational interventions designed using experiential learning theory. Registered nurses had the option of attending one or all three educational interventions on WFPB nutrition and CAD. Results: Eighty-six RNs working in cardiology specialties on three inpatient or one outpatient cardiac units at a large southeastern hospital system participated. The nurses believed CAD is a serious diagnosis (72/72) and that WFPB dietary patterns are cardioprotective for the prevention and management of CAD (63/72). However, nurse dietary behaviors were incongruent with their beliefs as some RNs (14/72) indicated they did not consume any vegetarian or fully plant-based meals. The most common barrier (36/72) to nurses adopting a WFPB dietary pattern was a taste preference for meat and animal products. Half of the eight nurses who completed at least one of the educational interventions and the postsurvey reported increased confidence to advise patients with CAD on the WFPB dietary pattern. Combined, participants self-reported their vegetarian or fully plant-based meal frequency increased slightly. Discussion: Registered nurses lack a working knowledge of WFPB eating patterns in their personal and professional lives, which may impact the quality of dietary education they provide to people with CAD or MI. Overcoming barriers to education on WFPB dietary patterns is important for increasing nurse confidence in teaching people with CAD about this evidence-based dietary health behavior. Conclusion: Registered nurses’ knowledge and perceptions of WFPB eating patterns may be enhanced through professional development activities. RNs may be more likely to engage with education that is frequent, brief, asynchronous, and online or part of existing onboarding such as lunch and learn events to sample WFPB foods. Future research is needed on strategies to engage and empower RNs to educate people with CAD on WFPB nutrition.

Monocytes Reprogrammed by 4-PBA Potently Contribute to the Resolution of Inflammation and Atherosclerosis.

Chronic inflammation initiated by inflammatory monocytes underlies the pathogenesis of atherosclerosis. However, approaches that can effectively resolve chronic low-grade inflammation targeting monocytes are not readily available. The small chemical compound 4-phenylbutyric acid (4-PBA) exhibits broad anti-inflammatory effects in reducing atherosclerosis. Selective delivery of 4-PBA reprogrammed monocytes may hold novel potential in providing targeted and precision therapeutics for the treatment of atherosclerosis. Systems analyses integrating single-cell RNA sequencing and complementary immunologic approaches characterized key resolving characteristics as well as defining markers of reprogrammed monocytes trained by 4-PBA. Molecular mechanisms responsible for monocyte reprogramming were assessed by integrated biochemical and genetic approaches. The intercellular propagation of homeostasis resolution was evaluated by coculture assays with donor monocytes trained by 4-PBA and recipient naive monocytes. The in vivo effects of monocyte resolution and atherosclerosis prevention by 4-PBA were assessed with the high-fat diet-fed ApoE-/- mouse model with IP 4-PBA administration. Furthermore, the selective efficacy of 4-PBA-trained monocytes was examined by IV transfusion of ex vivo trained monocytes by 4-PBA into recipient high-fat diet-fed ApoE-/- mice. In this study, we found that monocytes can be potently reprogrammed by 4-PBA into an immune-resolving state characterized by reduced adhesion and enhanced expression of anti-inflammatory mediator CD24. Mechanistically, 4-PBA reduced the expression of ICAM-1 (intercellular adhesion molecule 1) via reducing peroxisome stress and attenuating SYK (spleen tyrosine kinase)-mTOR (mammalian target of rapamycin) signaling. Concurrently, 4-PBA enhanced the expression of resolving mediator CD24 through promoting PPARγ (peroxisome proliferator-activated receptor γ) neddylation mediated by TOLLIP (toll-interacting protein). 4-PBA-trained monocytes can effectively propagate anti-inflammation activity to neighboring monocytes through CD24. Our data further demonstrated that 4-PBA-trained monocytes effectively reduce atherosclerosis pathogenesis when administered in vivo. Our study describes a robust and effective approach to generate resolving monocytes, characterizes novel mechanisms for targeted monocyte reprogramming, and offers a precision therapeutics for atherosclerosis based on delivering reprogrammed resolving monocytes.

Comparative Prognostic Value of Coronary Calcium Score and Perivascular Fat Attenuation Index in Coronary Artery Disease.

Coronary artery disease (CAD) is the leading global cause of mortality, accounting for approximately 30% of all deaths. It is primarily characterized by the accumulation of atherosclerotic plaques within the coronary arteries, leading to reduced blood flow to the heart muscle. Early detection of atherosclerotic plaques is crucial to prevent major adverse cardiac events. Notably, recent studies have shown that 15% of myocardial infarctions occur in patients with non-obstructive CAD, underscoring the importance of comprehensive plaque assessment beyond merely identifying obstructive lesions. Cardiac Computed Tomography Angiography (CCTA) has emerged as a cost-effective and efficient technique for excluding obstructive CAD, particularly in patients with a low-to-intermediate clinical likelihood of the disease. Recent advancements in CCTA technology, such as improved resolution and reduced scan times, have mitigated many technical challenges, allowing for precise quantification and characterization of both calcified and non-calcified atherosclerotic plaques. This review focuses on two critical physiological aspects of atherosclerotic plaques: the burden of calcifications, assessed via the coronary artery calcium score (CACs), and perivascular fat attenuation index (pFAI), an emerging marker of vascular inflammation. The CACs, obtained through non-contrast CT scans, quantifies calcified plaque burden and is widely used to stratify cardiovascular risk, particularly in asymptomatic patients. Despite its prognostic value, the CACs does not provide information on non-calcified plaques or inflammatory status. In contrast, the pFAI, derived from CCTA, serves as an indirect marker of coronary inflammation and has shown potential in predicting adverse cardiac events. Combining both CACs and pFAI assessment could offer a comprehensive risk stratification approach, integrating the established calcification burden with novel inflammatory markers to enhance CAD prevention and management strategies.

Time-Restricted Feeding Reduces Atherosclerosis in LDLR KO Mice but Not in ApoE Knockout Mice.

Dyslipidemia increases cardiovascular disease risk, the leading cause of death worldwide. Under time-restricted feeding (TRF), wherein food intake is restricted to a consistent window of <12 hours, weight gain, glucose intolerance, inflammation, dyslipidemia, and hypercholesterolemia are all reduced in mice fed an obesogenic diet. LDLR (low-density lipoprotein receptor) mutations are a major cause of familial hypercholesterolemia and early-onset cardiovascular disease. We subjected benchmark preclinical models, mice lacking LDLR-knockout or ApoE knockout to ad libitum feeding of an isocaloric atherogenic diet either ad libitum or 9 hours TRF for up to 13 weeks and assessed disease development, mechanism, and global changes in hepatic gene expression and plasma lipids. In a regression model, a subset of LDLR-knockout mice were ad libitum fed and then subject to TRF. TRF could significantly attenuate weight gain, hypercholesterolemia, and atherosclerosis in mice lacking the LDLR-knockout mice under experimental conditions of both prevention and regression. In LDLR-knockout mice, increased hepatic expression of genes mediating β-oxidation during fasting is associated with reduced VLDL (very-low-density lipoprotein) secretion and lipid accumulation. Additionally, increased sterol catabolism coupled with fecal loss of cholesterol and bile acids contributes to the atheroprotective effect of TRF. Finally, TRF alone or combined with a cholesterol-free diet can reduce atherosclerosis in LDLR-knockout mice. However, mice lacking ApoE, which is an important protein for hepatic lipoprotein reuptake do not respond to TRF. In a preclinical animal model, TRF is effective in both the prevention and regression of atherosclerosis in LDLR knockout mice. The results suggest TRF alone or in combination with a low-cholesterol diet can be a lifestyle intervention for reducing cardiovascular disease risk in humans.

Association of Physical Activity Levels with Coronary Artery Disease Risk Factors in Middle aged (40-55) Bangladeshi Women

Background: A sedentary lifestyle is associated with increased risk of Coronary Artery Disease (CAD) in women. At least 150min/wk of moderate activity or 75min/wk of vigorous activity or combination is recommended by American Heart Association (AHA) for primary prevention of CAD. The purpose of this study was to assess the physical activity levels of middle aged women and to find out the association of CAD risk factors with physical activity level. Methods: This cross-sectional analytical study was conducted in Dhaka Medical College Hospital (DMCH) cardiology OPD from May 2019 to April 2020. We interviewed 249 middle aged women (40-55) who attended our OPD during the study period and fulfilled the exclusion and inclusion criteria. Global Physical Activity Questionnaire (GPAQ) was used to assess physical activity level. Blood pressure and BMI was measured. OGTT and fasting lipid profile was done. Subjects with low physical activity was assigned in Group I (n=152), moderate activity in group II (n= 93) and high activity in group III (n= 4). Association between the physical activity levels and presence of CAD risk factors like DM, HTN, dyslipidemia and obesity was evaluated. Results: In this study we found that most of the study subjects (61.0%) were in low active group. Overall 70.2% women were menopausal and premature menopause (≤50 years) was found in 47.8% of subjects. Mean age of menopause was 47±3.8; (44-53) years and mean duration of menopause was 3.1±0.5 years. Overall prevalence of DM, HTN, obesity and dyslipidemia was 62.2%, 50.6%, 39.8% and 53.4% accordingly. Women in low active group were having significant higher proportion of DM (52.6%), HTN (65.8%), obesity (57.9%) and dyslipidemia (75.7%) in comparison to moderate active group. Only 4 women were in highly active group and none of the CAD risk factors was present among them. Bangladesh Heart Journal 2024; 39(2): 127-137

Achieving Successful Prevention of Coronary Artery Disease: A Worldwide Call to Action.

Achieving Successful Prevention of Coronary Artery Disease: A Worldwide Call to Action.

Behavioral, Clinical, and Coronary Artery Calcium Screening for Prevention and Treatment of Subclinical Atherosclerosis: Implications for Health Education

ABSTRACT Background In the USA, heart disease is the leading cause of death for women and men. Coronary artery disease (CAD) is the most common type of heart disease. Purpose To investigate the association between behavioral and non-behavioral risk factors associated with subclinical atherosclerosis. Methods Patients referred for a CT angiography completed a demographic/behavioral questionnaire and medical history interview for CAD risk factors. Risk factor data were correlated with CAD subclinical atherosclerosis scores for 521 participants. Results Frequency among four levels of CAD revealed: no disease 38%, mild atherosclerotic 20%, moderate atherosclerotic 30%, and severe atherosclerosis 12%. Significant (p ≤ .05) demographic variables were as follows: age, race, marital status, and employment status. Significant predictive behavioral variables were as follows: tobacco use, daily water intake, sodium consumption, exercise days per week, and junk food consumption. Risk factors significantly associated with subclinical CAD included hypertension, diabetes, sleep apnea, and abnormal coronary calcium score. Discussion Multi-slice CT angiography allows early reliable evaluation of subclinical atherosclerosis and correlation with behavioral/non-behavioral risk factors with level of CAD, instrumental to primary and secondary CAD prevention, limiting tertiary CAD treatment. Translation to Health Education Practice Study results have implications for Health Educators with regard to intervention research planning, implementation, and evaluation.

Use of Olives-derived Phytochemicals for Prevention and Treatment of Atherosclerosis: An Update.

Mediterranean diet is frequently associated with longevity and a lower incidence of adverse cardiovascular events because of the biological activities and health effects of olives - its key component. Olive oil, olive leaf extract, fruits and different by-products contain many bioactive components that exert anti-oxidant, anti-inflammatory and anti-apoptotic activities. In this review, we focus on the recent studies exploring molecular mechanisms underlying the cardioprotective properties of different olive oils, olive leave extracts, and specific micro-constituents (such as oleuropein, tyrosol, hydroxytyrosol and others) in vitro on rodent models and in clinical trials on human subjects. Particularly, hydroxytyrosol and oleuropein were identified as the major bioactive compounds responsible for the antioxidant, anti-inflammatory, anti-platelet aggregation and anti-atherogenic activities of olive oil. In total, the discussed results demonstrated a positive association between the consumption of olive oil and improvement in outcomes in atherosclerosis, diabetes, myocardial infarction, heart failure, hypertension and obesity.

Assessing the causal relationship between metabolic biomarkers and coronary artery disease by Mendelian randomization studies

The development of coronary artery disease (CAD) is significantly affected by impaired endocrine and metabolic status. Under this circumstance, improved prevention and treatment of CAD may result from knowing the connection between metabolites and CAD. This study aims to delve into the causal relationship between human metabolic biomarkers and CAD by using two-sample Mendelian randomization (MR). Utilizing two-sample bidirectional MR analysis, we assessed the correlation between 1400 blood metabolites and CAD, and the metabolites data from the CLSA, encompassing 8299 participants. Metabolite analysis identified 1091 plasma metabolites and 309 ratios as instrumental variables. To evaluate the causal link between metabolites and CAD, we analyzed three datasets: ebi-a-GCST005195 (547,261 European & East Asian samples), bbj-a-159 (29,319 East Asian CAD cases & 183,134 East Asian controls), and ebi-a-GCST005194 (296,525 European & East Asian samples). To estimate causal links, we utilized the IVW method. To conduct sensitivity analysis, we used MR-Egger, Weighted Median, and MR-PRESSO. Additionally, we employed MR-Egger interception and Cochran’s Q statistic to assess potential heterogeneity and pleiotropy. What’s more, replication and reverse analyses were performed to verify the reliability of the results and the causal order between metabolites and disease. Furthermore, we conducted a pathway analysis to identify potential metabolic pathways. 59 blood metabolites and 27 metabolite ratios nominally associated with CAD (P < 0.05) were identified by IVW analysis method. A total of four known blood metabolites, namely beta-hydroxyisovaleroylcarnitine (OR 1.06, 95% CI 1.027–1.094, FDR 0.07), 1-palmitoyl-2-arachidonoyl (OR 1.07, 95% CI 1.029–1.110, FDR 0.09), 1-stearoyl-2- docosahexaenoyl (OR 1.07, 95% CI 1.034–1.113, FDR 0.07) and Linoleoyl-arachidonoyl-glycerol, (OR 1.07, 95% CI 1.036–1.105, FDR 0.05), and two metabolite ratios, namely spermidine to N-acetylputrescine ratio (OR 0.94, 95% CI 0.903–0.972, FDR 0.09) and benzoate to linoleoyl-arachidonoyl-glycerol ratio (OR 0.87, 95% CI 0.879–0.962, FDR 0.07), were confirmed as having a significant causal relationship with CAD, after correcting for the FDR method (p < 0. 1). A causal relationship was found to be established between beta -hydroxyisovalerylcarnitine and CAD with the validation in other two datasets. Moreover, multiple metabolic pathways were discovered to be associated with CAD. Our study supports the hypothesis that metabolites have an impact on CAD by demonstrating a causal relationship between human metabolites and CAD. This study is important for new strategies for the prevention and treatment of CAD.

Primary Prevention of Coronary and Other Cardiovascular Diseases: A Focused Review.

In 2022, the Japan Atherosclerosis Society (JAS) updated its prevention guidelines, the "Japan Atherosclerosis Society (JAS) Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2022" (JAS2022GL), expanding its scope from coronary artery disease (CAD) to atherosclerotic cardiovascular diseases (ASCVDs), including atherothrombotic stroke. The following year, the Japanese Circulation Society (JCS) updated its guidelines for primary prevention entitled "JCS 2023 Guideline on the Primary Prevention of Coronary Artery Disease" (JCS2023GL). Since those publications, scientific advancements in relevant fields have continued. This review article outlines the current recommendations provided by the guidelines, provides background information supporting these recommendations, introduces scientific findings subsequent to prior publications, and discusses future directions on select topics for the primary prevention of CVD. The topics covered in this review are traditional risk factors, including dyslipidemia and hypertension, the application of comprehensive risk stratification or risk scoring systems, patient-specific topics, salt and alcohol, and environmental factors. These topics were deliberate and selected by the authors, who were involved in the compilation of either or both JAS2022GL and JCS2023GL. This review not only emphasizes the pivotal role of continuously updated guidelines in shaping clinical practice but also stresses the urgent need for ongoing research to bridge existing knowledge and practice gaps.

Effect of mindfulness-based interventions on anxiety, depression, and stress in patients with coronary artery disease: a systematic review and meta-analysis of randomized controlled trials.

Adopting lifestyle interventions is pivotal in coronary artery disease (CAD) management and prevention to amplify cardiovascular and mental well-being. This study aims to quantify the effect of mindfulness-based interventions (MBIs) on anxiety, depression and stress in CAD patients. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted by searching four electronic databases (PubMed, CENTRAL, Scopus, and Science Direct) through December 2023. The risk of bias was assessed using the PEDro tool, and the study outcomes were expressed as standard mean difference at 95% CI. Out of 1838 yielded results, eight RCTs involving 623 participants with a mean age of 56.96 ± 4.89 met the prespecified eligibility criteria. The pooled results showed a statistically significant and beneficial effect of MBIs on CAD patients' mental health status in regards to anxiety (SMD = -0.83; 95% CI [-1.19, -0.46], p < 0.001), depression (SMD = - 0.86; 95% CI [-1.14, -0.58], p < 0.001), and stress (SMD = -0.69; 95% CI [-1.27, -0.12], p = 0.02). The subgroup sensitivity analyses based on the region (Asia vs. Europe) indicated a statistically non-significant subgroup effect of MBIs on anxiety (I 2 = 63.9%, p = 0.10) and depression (I 2 = 25.8%, p = 0.25), and a significant effect on stress (I 2 = 80.0%, p = 0.03). Although the methodological quality of the trials was generally satisfactory, all studies lacked allocation concealment and blinding. Additionally, gender imbalances, and inadequate follow-up may have potentially compromised the validity of the trials. Mindfulness-based interventions are beneficial for improving CAD patients' anxiety, depression and stress symptoms. Nevertheless, it is imperative to conduct more rigorous and robust studies with an equal gender ratio and long-term follow-up.

Current and Emerging Approaches for Primary Prevention of Coronary Artery Disease Using Cardiac Computed Tomography.

To summarize the current use of cardiac computed tomography (CT) technologies as well as their pertinent evidence in regards to prevention of coronary artery disease (CAD). Cardiac CTA has now become a main non-invasive method for the evaluation of symptomatic CAD. In addition to coronary calcium score, other CT technologies such as atherosclerotic plaque analysis, fractional flow reserve estimation by CT, pericoronary fat attenuation, and endothelial wall shear stress have emerged. Whether the use of CT modalities can enhance risk prediction and prevention in CAD has not been fully answered. We discuss the evidence for coronary artery calcium scoring and coronary CT angiography in primary prevention and the current barriers to their use. We attempt to delineate what can be done to expand use and what studies are needed to broaden adoption in the future. We also examine the potential roles of emerging CT technologies. Finally, we describe potential clinical approaches to prevention that would incorporate cardiac CT technologies.

Association between Interleukin-6 and Multiple Acute Infarctions in Symptomatic Intracranial Atherosclerotic Disease.

Interleukin-6 (IL-6) plays an important role in the pathophysiology of atherosclerosis. This study aimed to determine whether IL-6 is a crucial biomarker associated with Multiple Acute Infarctions (MAIs), which indicate an important stroke mechanism of artery-- to-artery embolism with a high risk of stroke recurrence in symptomatic Intracranial Atherosclerotic Disease (sICAD). We tested the association between circulating IL-6 levels and the presence of MAIs in a prospective population-based registry. We included 1,919 patients with sICAD and baseline IL-6 levels from the Third China National Stroke Registry for the current analysis, The baseline IL-6 was centrally measured at Beijing Tiantan Hospital, Images of the brain parenchyma and vascular structures were digitized and then blindly and independently read by two groups of trained readers, The recruited patients were divided into 3 groups according to IL-6 tertiles, The relationship between baseline IL-6 tertile levels and the presence of MAIs was modeled using multivariate logistic regression. Compared to patients in the first IL-6 tertile those in the second and third tertiles demonstrated a significantly higher proportion of MAIs. The odds ratios were 1.81 [95% Confidence Interval (CI), 1.42-2.30] for the second versus first tertile and 2.15 (95% CI 1.66-2.79) for the third versus first tertile, The proportion of patients with MAIs increased with rising IL-6 tertiles observed at 59.3%, 71.6% and 76.4% for the first, second and third tertiles, respectively (P for trend < 0.001). The association between higher IL-6 tertiles and increased proportion of MAIs was also present in subgroups defined by age < 65 years, age ≥ 65 years, male, and high-sensitivity C-reactive Protein (hs-CRP) ≥ 2 mg/L. Furthermore, a significant interaction was detected for the hs- CRP subgroup (P = 0.038). In sensitivity analyses, the positive correlation between IL-6 levels and the proportion of MAIs remained consistent. In patients with sICAD, higher IL-6 levels were associated with an increased proportion of MAIs. IL-6 could be used as a biomarker and a potential therapeutic target for future atherosclerosis treatment and prevention in patients with sICAD.

Exploring the Molecular Mechanism of Schisandrin C for the Treatment of Atherosclerosis via the PI3K/AKT/mTOR Autophagy Pathway.

Atherosclerosis (AS) is a common cardiovascular disease that poses a major threat to health. Schisandra chinensis is a medicinal and edible plant that is commonly used to treat cardiovascular diseases. In this paper, HPLC was used to detect and analyze 5 different components in Schisandra chinensis. Network pharmacological predictions highlight the PI3K/AKT/mTOR pathway as an important pharmacological pathway. The effective ingredient Schisandrin C was screened by the molecular docking technique. ox-LDL-induced HUVECs were used to construct the atherosclerosis model for further experimental verification. The results showed that Schisandrin C interfered with the PI3K/AKT/mTOR autophagy pathway. This study lays a foundation for the further application of Schisandrin C in the prevention and treatment of atherosclerosis in the future.

Vascular endothelial cells of Mongolian gerbils are resistant to cholesterol-induced mitochondrial dysfunction and oxidative damage.

Atherosclerosis is essentially the leading factor behind occurrences of cardiovascular diseases (CVDs)-associated incidents, while mitochondrial dysfunction is also the main cause of atherosclerosis. The present study conducted a comparative analysis of mitochondrial function-related indicators in cholesterol-induced vascular endothelial cells (VECs) from Mongolian gerbils, Sprague-Dawley (SD) rats and humans. It reported that the inhibitory effect of cholesterol treatment on the viability of Mongolian gerbil VECs was markedly lower than the other two types of VECs at the same concentration. Following cholesterol treatment, mitochondrial DNA copy numbers, reactive oxygen species level, calcium concentration and mitochondrial membrane potential of Mongolian gerbil VECs did not change markedly. These results suggested that the function of mitochondria in the VECs of Mongolian gerbil is normal. Additionally, cholesterol treatment also did not alter the levels of superoxide dismutase, glutathione peroxidase, ATP, NADH-CoQ reductase and cytochrome c oxidase in Mongolian gerbil VECs. It was hypothesized that the VECs of Mongolian gerbils have certain resistance to oxidative damage induced by cholesterol. In brief, the present study demonstrated that VECs of Mongolian gerbils are resistant to cholesterol-induced mitochondrial dysfunction and oxidative damage. The aforementioned findings establish a theoretical foundation for the advancement of innovative strategies in the prevention and treatment of atherosclerosis.

Progression in the Relationship between Exosome Production and Atherosclerosis.

Atherosclerosis (AS) is the leading cause of cardiovascular disease, causing a major burden on patients as well as families and society. Exosomes generally refer to various lipid bilayer microvesicles originating from different cells that deliver various bioactive molecules to the recipient cells, exerting biological effects in cellular communication and thereby changing the internal environment of the body. The mechanisms of correlation between exosomes and the disease process of atherosclerosis have been recently clarified. Exosomes are rich in nucleic acid molecules and proteins. For example, the exosome miRNAs reportedly play important roles in the progression of atherosclerotic diseases. In this review, we focus on the composition of exosomes, the mechanism of their biogenesis and release, and the commonly used methods for exosome extraction. By summarizing the latest research progress on exosomes and atherosclerosis, we can explore the advances in the roles of exosomes in atherosclerosis to provide new ideas and targets for atherosclerosis prevention, diagnosis, and treatment.

β-Cyclodextrin and Hyaluronic Acid-Modified Targeted Nanodelivery System for Atherosclerosis Prevention.

Natural products have been widely recognized in clinical treatment because of their low toxicity and high activity. It is worth paying attention to modifying the biopolymer into nanostructures to give natural active ingredients additional targeting effects. In this study, based on the multifunctional modification of β-cyclodextrin (β-CD), a nanoplatform encapsulating the unstable drug (-)-epicatechin gallate (ECG) was designed to deliver to atherosclerotic plaques. Acetalization cyclodextrin (PH-CD), which responds to low-pH environments, and hyaluronic acid cyclodextrin, which targets the CD44 receptor on macrophage membranes, were synthesized from β-CD and hyaluronic acid using acetalization and transesterification, respectively. The resulting dual-carrier nanoparticles (Double-NPs) loaded with ECG were prepared using a solvent evaporation method. The Double-NPs effectively scavenged reactive oxygen species, promoted macrophage migration, inhibited macrophage apoptosis, and suppressed abnormal proliferation and migration of vascular smooth muscle cells. Furthermore, the Double-NPs actively accumulated in atherosclerotic plaques in ApoE-/- mice fed with a high-fat diet, leading to a reduced plaque area, inflammatory infiltration, and plaque instability. Our findings demonstrate that the newly developed ECG nanopreparation represents an effective and safe nanotherapy for diseases such as atherosclerosis.

Bixin, a New Atheroprotective Carotenoid Candidate, Prevents oxLDL-Induced Cytotoxicity and Mitochondrial Dysfunction in Macrophages: Involvement of the Nrf2 and NF-κB Pathways.

The accumulation of oxidized low-density lipoprotein (oxLDL) and its toxicity in the arterial wall have been implicated in atherosclerosis. This study aimed to investigate the mechanisms underlying the atheroprotective effect of bixin, a carotenoid obtained from the seeds of the tropical plant Bixa orellana, on Cu2+-induced LDL oxidation and oxLDL-mediated effects in J774A.1 macrophage cells. Bixin's effects were compared to those of lycopene, a carotenoid widely studied for its cardiovascular protective effects. LDL was isolated from human plasma, incubated with bixin or lycopene (positive control), and subjected to oxidation with CuSO4. Afterward, bixin or lycopene was incubated with J774A.1 macrophage cells and exposed to oxLDL. The levels of ROS, RNS, GSH, nitrite, mitochondrial function, and foam cell formation, as well as the expression of proteins related to the antioxidant and inflammatory status, were evaluated. The effect of bixin in inhibiting in vitro human-isolated LDL oxidation was more potent (5-6-fold) than that of lycopene. Bixin pretreatment reduced the atherogenic signaling triggered by oxLDL in the macrophages, namely the generation of reactive species, disturbance of nitric oxide homeostasis, mitochondrial dysfunction, and foam cell formation. The cytoprotective effects of bixin were accompanied by the upregulation of Nrf2 and the downregulation of the NF-kB pathways. Lycopene showed the same protective effect as bixin, except that it did not prevent mitochondrial dysfunction. The efficient performance of bixin makes it an ideal candidate for further trials as a new nutraceutical compound for the prevention of atherosclerosis.

Which surrogate insulin resistance indices best predict coronary artery disease? A machine learning approach

BackgroundVarious surrogate markers of insulin resistance have been developed, capable of predicting coronary artery disease (CAD) without the need to detect serum insulin. For accurate prediction, they depend only on glucose and lipid profiles, as well as anthropometric features. However, there is still no agreement on the most suitable one for predicting CAD.MethodsWe followed a cohort of 2,000 individuals, ranging in age from 20 to 74, for a duration of 9.9 years. We utilized multivariate Cox proportional hazard models to investigate the association between TyG-index, TyG-BMI, TyG-WC, TG/HDL, plus METS-IR and the occurrence of CAD. The receiver operating curve (ROC) was employed to compare the predictive efficacy of these indices and their corresponding cutoff values for predicting CAD. We also used three distinct embedded feature selection methods: LASSO, Random Forest feature selection, and the Boruta algorithm, to evaluate and compare surrogate markers of insulin resistance in predicting CAD. In addition, we utilized the ceteris paribus profile on the Random Forest model to illustrate how the model’s predictive performance is affected by variations in individual surrogate markers, while keeping all other factors consistent in a diagram.ResultsThe TyG-index was the only surrogate marker of insulin resistance that demonstrated an association with CAD in fully adjusted model (HR: 2.54, CI: 1.34–4.81). The association was more prominent in females. Moreover, it demonstrated the highest area under the ROC curve (0.67 [0.63–0.7]) in comparison to other surrogate indices for insulin resistance. All feature selection approaches concur that the TyG-index is the most reliable surrogate insulin resistance marker for predicting CAD. Based on the Ceteris paribus profile of Random Forest the predictive ability of the TyG-index increased steadily after 9 with a positive slope, without any decline or leveling off.ConclusionDue to the simplicity of assessing the TyG-index with routine biochemical assays and given that the TyG-index was the most effective surrogate insulin resistance index for predicting CAD based on our results, it seems suitable for inclusion in future CAD prevention strategies.