Obesity is associated with acute kidney injury in ST-segment-elevation myocardial infarction undergoing percutaneous coronary intervention: A national representative cohort study.

BACKGROUND: Acute kidney injury (AKI) is a frequent and potentially life-threatening complication after percutaneous coronary intervention (PCI) in patients with ST-segment-elevation myocardial infarction (STEMI). However, the relationship between obesity and the risk of AKI in this specific patient population has not been previously examined. METHODS: We queried the National Inpatient Sample (2016-2019) using ICD-10 codes to obtain a sample of adults with STEMI undergoing PCI. All patients were further subcategorized into obese and nonobese cohorts. The primary outcome was the incidence of AKI. Multivariate regression analysis was performed to assess the impact of obesity on AKI. The consistency of this correlation between subgroups was investigated using subgroup analysis and interaction testing. RESULTS: A total of 62,599 (weighted national estimate of 529,016) patients were identified, of which 9.80% (n = 6137) had AKI. Obesity comprised 19.78% (n = 1214) of the AKI cohort. Obese patients were on average younger, male, white, and had more comorbidities. Additionally, there was a significant positive association between obesity and AKI incidence (adjusted odds ratio [aOR]: 1.24, 95% confidence interval [CI]: 1.15-1.34), which was more pronounced in female patients (aOR: 1.56, 95% CI: 1.33-1.82, p < 0.001, p-interaction = 0.008). The AKI incidence in these patients increased steadily during the 4-year study period, and it was consistently higher in obese patients than in nonobese patients (p-trend < 0.001 for all). CONCLUSIONS: Obesity was independently associated with a greater risk of AKI among adults with STEMI undergoing PCI, particularly in female patients.

Symptomatic HIV infection and in-hospital outcomes for patients with acute myocardial infarction undergoing percutaneous coronary intervention from national inpatient sample.

Human immunodeficiency virus (HIV) infection increases the risk of acute myocardial infarction (AMI). However, little is known about its association with in-hospital outcomes and temporal trends in patients with AMI undergoing percutaneous coronary intervention (PCI). We queried patients with AMI who underwent PCI from the National Inpatient Sample Database (2003-2015) and stratified them into three groups: symptomatic, asymptomatic, and HIV-negative. After 1:2 case-control matching (CCM), logistic regression analysis was conducted to determine how HIV infection affected in-hospital outcomes. We also evaluated their recent trends from 2003 to 2015. The total weighted national estimate of 2,191,129 AMI cases included 2,178,995 HIV/AIDS-negative, 4994 asymptomatic, and 7140 symptomatic HIV cases. Symptomatic but not asymptomatic patients with HIV suffered more than triple the in-hospital mortality (adjusted odds ratio (aOR) 3.6, 95% confidence interval (CI) 2.5-5.2), over one-fold incidence of acute kidney injury (aOR 2.6 95% CI 1.9-3.4) and cardiogenic shock risk (aOR 1.9, 95% CI 1.3-2.7), a longer length of hospital stay (beta 1.2, 95% CI 1.0-1.5), and had more procedures (beta 1.3, 95% CI 1.2-1.5). These disparities relating to symptomatic HIV infection persisted from 2003 to 2015. In patients with AMI who underwent PCI, symptomatic HIV infection was associated with higher in-hospital mortality and more severe outcomes.

The non-linear association between ascending aorta diameter and risk of 12-month mortality in Chinese patients with heart failure: A retrospective cohort study.

Background: There is no conclusive proven link between ascending aorta diameter (AoD) and the risk of death from heart failure (HF). As a result, a retrospective cohort analysis was carried out to determine whether AoD is associated with 12-month mortality in Chinese HF patients. Methods: From January 2017 to March 2020, we collected data on 575 Chinese patients with HF. The exposure and outcome variables were baseline AoD and 12-month risk of mortality (all-cause + cardiac origin), respectively. Data on demographics, drug usage, clinical characteristics, recognized indicators of HF, and comorbidities were included as covariates. To investigate the independent relationships of AoD with the risk of 12-month death, binary logistic regression and two-piecewise linear models were utilized. Results: Our findings imply that there was a non-linear relationship between AoD and the risk of 12-month mortality. For the AoD range of 23 to 37, there was no association with the risk of cardiac mortality [odds ratio (OR) 0.78, 95% confidence interval (CI), 0.62-1.04]. In the AoD range of 37-49, however, the risk of 12-month cardiac death increased by approximately 70% for every 1 mm increase in AoD (OR 1.70, 95% CI, 1.13-2.55). When all-cause death was chosen as the outcome, the same outcome was shown. Conclusion: An AoD larger than 37 mm is a hazardous threshold for Chinese HF patients. Beyond this limit increased the risk of cardiac death by 70% for every 1 mm increase in AoD.

Attenuated cell-cycle division protein 2 and elevated mitotic roles of polo-like kinase 1 characterize deficient myoblast fusion in peripheral arterial disease.

INTRODUCTION: We propose that MuSC-derived myoblasts in PAD have transcriptomic differences that can highlight underlying causes of ischemia-induced myopathy. METHODS: Differentiation capacity among perfused and ischemic human myoblasts was compared. Following next generation sequencing of mRNA, Ingenuity Pathway Analysis (IPA) was performed for canonical pathway enrichment. Live cell imaging and immunofluorescence were performed to determine myocyte fusion index and protein expression based on insights from IPA, specifically concerning cell cycle regulators including cell-division cycle protein 2 (CDC2) and polo-like kinase 1 (PLK1). RESULTS: Ischemic myoblasts formed attenuated myotubes indicative of reduced fusion. Additionally, myoblasts from ischemic segments showed significant differences in canonical pathways associated with PLK1 (upregulated) and G2/M DNA damage checkpoint regulation (downregulated). PLK1 inhibition with BI2536 did not affect cell viability in any group over 24 h but deterred fusion more significantly in PAD myoblasts. Furthermore, PLK1 inhibition reduced the expression of checkpoint protein CDC2 in perfused but not ischemic cells. CONCLUSION: Differentiating myoblasts derived from ischemic muscle have significant differences in gene expression including those essential to DNA-damage checkpoint regulation and cell cycle progress. DNA-damage checkpoint dysregulation may contribute to myopathy in PAD.

Symptomatic human immunodeficiency virus infection is associated with advanced presentation and perioperative mortality in patients undergoing surgery for peripheral arterial disease.

OBJECTIVE: Prior studies have demonstrated an increased risk of developing cardiovascular and peripheral arterial disease (PAD) in patients with human immunodeficiency virus (HIV). However, the effect of chronic HIV infection in patients with preexisting PAD and requiring vascular intervention is unclear. In the present study, we assessed the differences in clinical presentation and perioperative outcomes for patients with PAD who had undergone revascularization or amputation with and without HIV infection. METHODS: International Classification of Diseases, 9th and 10th Revisions, Clinical Modification, codes were used to identify patients with a prior diagnosis of PAD who had undergone lower extremity revascularization or amputation in the National Inpatient Sample (2003-2017). From this group, the patients were divided for analysis into those with and without HIV infection. Of the patients with HIV infection (PWHs), we identified additional subsets of patients: those with any prior or current diagnosis of an HIV-related illness, including acquired immunodeficiency syndrome, designated as symptomatic HIV, and those without such a diagnosis, designated as asymptomatic HIV infection. Propensity score matching was performed to create matched cohorts. Population-based comparative analyses were performed of the clinical characteristics of the HIV-infected and HIV-uninfected groups. Univariate and multivariate logistic regression analyses of the perioperative in-hospital outcomes were performed on the matched cohorts. RESULTS: A total of 224,912 patients aged 18 to 85 years were identified who had been admitted with an established diagnosis of PAD and had undergone a lower extremity procedure. Of these patients, 1264 (0.56%) also had a diagnosis of HIV infection. Symptomatic PWHs were more likely to present with critical limb ischemia than were the HIV-uninfected patients or asymptomatic PWHs (66.2% vs 46.3% and 43.6%; P < .01). However, both asymptomatic and symptomatic PWHs were more likely to have required minor (7.5% and 6.7% vs 2.6%; P < .01) and major (12.9% and 27.4% vs 7.0%; P < .01) amputations than were matched HIV-uninfected controls. Although adjusted multivariate logistic regression analysis demonstrated symptomatic HIV infection to be a significant, independent predictor of in-hospital mortality (odds ratio, 2.46; 95% confidence interval, 1.37-4.40; P = .003), the perioperative mortality for the asymptomatic PWH was comparable to that of matched HIV-uninfected controls. CONCLUSIONS: Symptomatic PWHs, including patients living with acquired immunodeficiency syndrome, who had required a PAD-related procedure had presented with more advanced vascular disease and were most at risk of early perioperative mortality. However, the presentation and mortality between asymptomatic PWHs with well-controlled disease and HIV-uninfected patients were comparable. All PWHs with PAD were more likely to undergo lower extremity amputations than were HIV-uninfected matched controls. Asymptomatic, well-controlled HIV infection should not be a contraindication to elective PAD-related procedures because the mortality was similar to that of HIV-uninfected controls. However, the limb salvage rates might be lower for all PWHs with PAD, regardless of HIV disease severity. Taken together, these findings can improve perioperative risk stratification and surgical management of PAD in this high-risk population.

Role of PCSK9 in Homocysteine-Accelerated Lipid Accumulation in Macrophages and Atherosclerosis in ApoE-/- Mice.

Background: Homocysteine (Hcy) has been established as an independent risk factor for atherosclerosis, and the involvement of hyperhomocysteinemia (HHcy) in atherosclerotic lesions is complex. Proprotein convertase subtilisin kexin 9 (PCSK9) has vital importance in lipid metabolism, and its inhibitors have intense lipid-lowering and anti-atherosclerotic effects. However, the underlying effect of PCSK9 on HHcy-accelerated dyslipidemia of macrophages is still uncertain. The purpose of this study was to investigate the potential role of PCSK9 in Hcy-induced lipid accumulation and atherosclerotic lesions. Methods: In vitro, gene and protein expressions were assessed by real-time quantitative PCR and western blot in THP-1 macrophages with Hcy incubation. Lipid accumulation and cholesterol efflux were evaluated with Hcy treatment. SBC-115076 was used to examine the role of PCSK9 in ATP-binding cassette transporter A1 and G1 (ABCA1 and ABCG1)-dependent cholesterol efflux. In vivo, lesion area, lipid deposition and collagen contents were determined in aortas of ApoE-/- mice under a methionine diet. SBC-115076 was subcutaneously injected to explore the potential effects of PCSK9 inhibition on alleviating the severity of HHcy-related atherosclerotic lesions. Results: In THP-1 macrophages, Hcy dose- and time-dependently promoted PCSK9 gene and protein levels without regulating the translation of Low-density lipoprotein receptor (LDLR). SBC-115076 used to inhibit PCSK9 largely alleviated lipid accumulation and reversed the cholesterol efflux to apolipoprotein-I(apoA-I) and high-density lipoprotein (HDL) mediated by ABCA1 and ABCG1. In ApoE-/- mice, methionine diet induced HHcy caused larger lesion area and more lipid accumulation in aortic roots. SBC-115076 reduced atherosclerotic severity by reducing the lesion area and lipid accumulation and increasing expressions of ABCA1 and ABCG1 in macrophages from atherosclerotic plaque. In addition, SBC-115076 decreased plasma Hcy level and lipid profiles significantly. Conclusion: PCSK9 promoted lipid accumulation via inhibiting cholesterol efflux mediated by ABCA1 and ABCG1 from macrophages and accelerated atherosclerotic lesions under HHcy treatment. Inhibiting PCSK9 may have anti-atherogenic properties in HHcy-accelerated atherosclerosis.

The regulation of Ero1-alpha in homocysteine-induced macrophage apoptosis and vulnerable plaque formation in atherosclerosis.

BACKGROUND AND AIMS: Hyperhomocysteinemia (HHcy) is an independent risk factor for atherosclerosis and plaque vulnerability. Macrophage apoptosis mediated by endoplasmic reticulum (ER) stress plays an important role in the pathogenesis of HHcy-aggravated atherosclerosis. Endoplasmic reticulum oxidoreductase 1α (Ero1α) is critical for ER stress-induced apoptosis. We hypothesized that Ero1α may contribute to ER-stress induced macrophage apoptosis and plaque stability in advanced atherosclerotic lesions by HHcy. METHODS: Apoe-/- mice were maintained on drinking water containing homocysteine (Hcy, 1.8 g/L) to establish HHcy atherosclerotic models. The role of Ero1α in atherosclerotic plaque stability, macrophage apoptosis and ER stress were monitored in the plaque of aortic roots in HHcy Apoe-/- mice with or without silence or overexpression of Ero1α through lentivirus. Mouse peritoneal macrophages were used to confirm the regulation of Ero1α on ER stress dependent apoptosis in the presence of HHcy. RESULTS: Atherosclerotic plaque vulnerability and macrophage apoptosis were promoted in Apoe-/- mice by high Hcy diet, accompanied by the upregulation of Ero1α expression and ER stress. Inhibition of Ero1α prevented macrophage apoptosis and atherosclerotic plaque vulnerability, and vice versa. Consistently, in mouse peritoneal macrophages, ER stress and apoptosis were attenuated by Ero1α deficiency, but enhanced by Ero1α overexpression. CONCLUSIONS: Hcy, via upregulation of Ero1α expression, activates ER stress-dependent macrophage apoptosis to promote vulnerable plaque formation in atherosclerosis. Ero1α may be a potential therapeutic target for atherosclerosis induced by Hcy.

Fibrosis Distinguishes Critical Limb Ischemia Patients from Claudicants in a Transcriptomic and Histologic Analysis.

Most patients with critical limb ischemia (CLI) from peripheral arterial disease (PAD) do not have antecedent intermittent claudication (IC). We hypothesized that transcriptomic analysis would identify CLI-specific pathways, particularly in regards to fibrosis. Derivation cohort data from muscle biopsies in PAD and non-PAD (controls) was obtained from the Gene Expression Omnibus (GSE120642). Transcriptomic analysis indicated CLI patients (N = 16) had a unique gene expression profile, when compared with non-PAD controls (N = 15) and IC (N = 20). Ninety-eight genes differed between controls and IC, 2489 genes differed between CLI and controls, and 2783 genes differed between CLI and IC patients. Pathway enrichment analysis showed that pathways associated with TGFß, collagen deposition, and VEGF signaling were enriched in CLI but not IC. Receiver operating curve (ROC) analysis of nine fibrosis core gene expression revealed the areas under the ROC (AUC) were all >0.75 for CLI. Furthermore, the fibrosis area (AUC = 0.81) and % fibrosis (AUC = 0.87) in validation cohort validated the fibrosis discrimination CLI from IC and control (all n = 12). In conclusion, transcriptomic analysis identified fibrosis pathways, including those involving TGFß, as a novel gene expression feature for CLI but not IC. Fibrosis is an important characteristic of CLI, which we confirmed histologically, and may be a target for novel therapies in PAD.

Usefulness of Morphology-Voltage-P-wave duration (MVP) score as a predictor of atrial fibrillation recurrence after pulmonary vein isolation.

BACKGROUND: Atrial fibrillation (AF) is known to be the most common arrhythmia, and the successful rate of long-term ablation can vary comparatively. Therefore, a clinical scoring system to predict rhythm outcome remains a critical unmet need. The electrocardiographic (ECG) risk score which is named Morphology-Voltage-P-wave duration (MVP) score was reported to be useful for predicting new-onset AF. The goal of the current study was to investigate whether the MVP score was a useful scheme in the prediction of rhythm outcome following pulmonary vein isolation (PVI) in paroxysmal atrial fibrillation (PAF). METHODS: We retrospectively analyzed baseline characteristics, risk scores, and rates of AF recurrence 12 months postablation in the medical records of 207 consecutive patients with PAF undergoing PVI in General Hospital of Ningxia medical University from 2010 to 2018. RESULTS: Two hundred and seven patients (71 females, median age 58.7 years) with symptomatic PAF underwent PVI. From the cohort, 32.3% (67) had a recurrence of AF within 1 year of the PVI. The area of the MVP score under the curve in the receiver operating characteristics (ROC) analysis was 0.789 (95% CI 0.730-0.840, p < .001). A score cut-off value of >3 showed the best predictive ability for AF recurrence within 1 year after PVI, with sensitivity (53.03%) and specificity (89.87%). CONCLUSIONS: The results of our study suggest that the easy-to-measure ECG MVP score can be used to predict recurrence of PAF after PVI.

Endothelial cell-specific deficiency of the adenosine deaminase ADAR1 aggravates LPS-induced lung injury in mice via an MDA5-independent pathway.

Adenosine deaminase acting on RNA 1 (ADAR1) has been shown to participate in the regulation of endothelial cells (ECs), as well as local and systemic inflammatory responses. Here, we find that bacterial lipopolysaccharide (LPS)-induced upregulation of ADAR1 in lung ECs is impaired in aged mice, an animal model with high rates of sepsis and mortality. Endothelial cell-specific ADAR1 knockout (ADAR1ECKO ) mice suffer from higher mortality rates, aggravated lung injury, and increased vascular permeability under LPS challenge. In primary ADAR1 knockout ECs, expression of the melanoma differentiation-associated gene 5 (MDA5), a downstream effector of ADAR1, is significantly elevated. MDA5 knockout completely rescues the postnatal offspring death of ADAR1ECKO mice. However, there is no reduction in mortality or apoptosis in lung cells of ADAR1ECKO /MDA5-/- mice challenged with LPS, indicating the involvement of an MDA5-independent mechanism in this process.

Low serum vitamin C correlates with an increased risk of peripheral arterial disease in current smokers: Results from NHANES 2003-2004.

BACKGROUND: Cigarette smoking is one of the most critical risk factors for peripheral arterial disease (PAD) and inversely correlated Vitamin C. Here we determine whether serum vitamin C correlates with the risk of PAD, especially among current smokers. METHODS: A cross-sectional analysis of 2383 individuals ≥40 y was performed from the U.S. National Health and Nutrition Examination Survey (NHANES 2003-2004), including measurement of ankle-brachial index (ABI), smoking status and serum vitamin C. We examined the interactions between plasma vitamin C and exposure to smoking on the risk of PAD. RESULTS: 912 (38.2%) were current smokers while 207 participants were diagnosed with PAD based on ABI(ABI≤0.9). Current smokers in the lowest vitamin C quartile had the highest prevalence of PAD (14.1%) compared to other quartiles. However, this trend was not significant in nonsmokers. Current smokers in the lowest quartile had a 2.32-fold risk (95% CI, 1.03-5.32; P = 0.04) for PAD after weighted adjustment for potential confounders, including vitamin D and C-reactive protein. In contrast, non-smokers did not have a differing risk of PAD as a function of vitamin C (P for interaction = 0.019). CONCLUSIONS: As an anti-oxidant and anti-inflammatory, low serum vitamin C appears to associates with the risk of PAD in smokers. A relationship between PAD and vitamin C in non-current smokers is not apparent. Modulating vitamin C in current smokers may help mitigate the risk of PAD and should be a target of mechanistic study.

Hyperhomocysteinemia induces vascular calcification by activating the transcription factor RUNX2 via Krüppel-like factor 4 up-regulation in mice.

One of the main characteristics of atherosclerosis is vascular calcification, which is linked to adverse cardiovascular events. Increased homocysteine (Hcy), a feature of hyperhomocysteinemia, is correlated with advanced vascular calcification and phenotypic switching of vascular smooth muscle cells (VSMCs). Oxidative stress and high phosphate levels also induce VSMC calcification, suggesting that the Krüppel-like factor 4 (KLF4) signaling pathway may also contribute to vascular calcification. In this study, we investigated this possibility and the role and mechanisms of Hcy in vascular calcification. We found that in atherosclerotic apolipoprotein E-deficient (ApoE-/-) mice, Hcy significantly increases vascular calcification in vivo, as well as VSMC calcification in vitro Of note, the Hcy-induced VSMC calcification was correlated with elevated KLF4 levels. Hcy promoted KLF4 expression in calcified atherosclerotic lesions in vivo and in calcified VSMCs in vitro shRNA-mediated KLF4 knockdown blocked the Hcy-induced up-regulation of runt-related transcription factor 2 (RUNX2) and VSMC calcification. RUNX2 inhibition abolished Hcy-induced VSMC calcification. Using ChIP analysis, we demonstrate that KLF4 interacts with RUNX2, an interaction promoted by Hcy stimulation. Our experiments also revealed that the KLF4 knockdown attenuates Hcy-induced RUNX2 transactivity, indicating that KLF4 is important in modulating RUNX2 transactivity. These findings support a role for Hcy in regulating vascular calcification through a KLF4-RUNX2 interaction and indicate that Hcy-induced, enhanced RUNX2 transactivity increases VSMC calcification. These insights reveal possible opportunities for developing interventions that prevent or manage vascular calcification.

Homocysteine accelerates atherosclerosis via inhibiting LXRα-mediated ABCA1/ABCG1-dependent cholesterol efflux from macrophages.

AIMS: Macrophage-derived foam-cell formation plays a crucial role in the development of atherosclerosis, and liver X receptor alpha (LXRα) is a key regulator of lipid metabolism in macrophages. Homocysteine (Hcy) is an independent risk factor of atherosclerosis; however, the regulation of lipid metabolism and role of LXRα induced by Hcy in macrophages is still unknown. The present study aimed to investigate the potential role of Hcy in disordered lipid metabolism and atherosclerotic lesions, especially the effects of Hcy on cholesterol efflux in macrophages and the possible mechanisms. MAIN METHODS: In vitro, lipid accumulation and cholesterol efflux were evaluated in THP-1 macrophages with Hcy intervention. Real-time quantitative PCR and western blot analyses were used to assess mRNA and protein levels. In vivo, atherosclerotic lesions and lipid profiles were evaluated by methionine diet-induced hyperhomocysteinemia (HHcy) in ApoE-/- mice. The LXRα agonist T0901317 was used to verify the role of LXRα in HHcy-accelerated atherosclerosis. KEY FINDINGS: Hcy promoted lipid accumulation and inhibited cholesterol efflux in THP-1 macrophages. HHcy mice showed increased lesion area and lipid accumulation in plaque. Both studies in vitro and in vivo showed decreased expression of ATP binding cassette transporter A1 (ABCA1) and G1 (ABCG1). T0901317 treatment increased ABCA1 and ABCG1 levels; reversed macrophage-derived foam-cell formation in THP-1 macrophages and reduced atherosclerotic lesions in ApoE-/- mice. SIGNIFICANCE: Inhibition of LXRα-mediated ABCA1/ABCG1-dependent cholesterol efflux from macrophages is a novel mechanism in Hcy-accelerated atherosclerosis.

Involvement of histone methylation in macrophage apoptosis and unstable plaque formation in methionine-induced hyperhomocysteinemic ApoE-/- mice.

AIMS: Hyperhomocysteinemia (Hhcy) is an independent risk factor of atherosclerosis and promotes unstable plaque formation. Epigenetic mechanisms play an important role in the pathogenesis of atherosclerosis induced by Hhcy. However, the exact mechanism is still undefined. Lesional apoptotic cells and necrotic core formation contribute greatly to the progression of plaque. The present study sought to determine whether modification of histone methylation is involved in macrophage apoptosis and unstable plaque formation in the condition of Hhcy. MATERIALS AND METHODS: The unstable plaque formation, lesional apoptotic cells and status of histone methylation were monitored in the aortas of Hhcy ApoE-/- mice induced by a high-methionine (HM) diet for 20weeks. Involvement of histone methylation in macrophage apoptosis and foam cell formation were assessed in macrophage Raw 264.7 cells after being challenged with homocysteine alone or in combination with the histone methylation inhibitor BIX 01294. KEY FINDINGS: The unstable plaque formation and lesion apoptotic cells are increased in ApoE-/- mice supplemented with high-methionine (HM), accompanied with a decreased expression of histone H3 lysine 9 dimethylation. Hhcy increases the apoptosis of macrophages and inhibits the histone H3 lysine 9 dimethylation, as well as the expression of histone methyltransferase G9a in vitro. Inhibition of histone methylation by BIX01294 enhances macrophage apoptosis and foam cell formation in vitro. SIGNIFICANCE: Our data suggest that Hhcy promotes the progression of atherosclerosis via macrophage apoptosis. Histone methylation might be involved in macrophage apoptosis and unstable plaque formation in methionine induced hyperhomocysteinemic ApoE-/- mice.

[Folic acid prevents Bcl-2 hypomethylation in rats with hyperhomocysteinemia].

OBJECTIVE: To investigate the effects of folic acid on Bcl-2 gene methylation status in rats with hyperhomocystinemia induced by ingestion of excess methionine. METHODS: 36 healthy 6-week-old wistar male rats, weighing (160 +/- 10) g, after being fed adaptable for one week, were randomly divided into control group (n = 12), hyperhomocysteinemia group (n = 12), folic acid treatment group (n = 12). The control group was fed with AIN-93G diet. The hyperhomocysteinemia group was fed with high-methionion diet, consisting of AIN-93G diet plus 1.7% methionion. The folic acid treatment group was fed with high-methionion plus folic acid-rich diet, consisting of AIN-93G diet plus 1.7% methionion and 0.008% folic acid. After be maintained for 18 weeks on the previously described diets, the concentrations in the plasma Hcy and folic acid and Vit B12 were measured with the IMX assays. The thoracic aorta was harvested for immunohist Chemical analysis. The methylation status of Bcl-2 gene was determined by nest touch-down PCR combined MSP(methylation specific PCR). Real-time RT PCR was used to detect mRNA expression of arotic Bcl-2. RESULTS: The study showed the following: (a) A high methionine diet for 18 weeks is sufficient to induce hyperhom degree Cystinemia; Folic acid supplementation to the rats fed the high-methionine diet prevented an elevation homocysteine (Hcy) levels in the plasma (P < 0.01 ). (b) Compared with the control group, the Hhcy group had a elevating Bcl-2 expression by immunohistochemical analysis in aorta, along with Bcl-2 hypomethylation (P < 0.05) and increased Bcl-2 mRNA expression (P < 0.05 ). (c) Most important, after folic acid supplementation, the lowering of Hcy levels was accompanied by a marked decreased Bcl-2 expression by immunohistochemical analysis and Bcl-2 hypermethylation (P < 0.05) and reduced Bcl-2 mRNA expression (P < 0.05). CONCLUSIONS: Folic acid supplementation can prevents Bcl-2 hypomethylation in rats with hyperhomocysteinemia, resulting in a decreased Bcl-2 expression.