Background:Hyperhomocysteinemia (HHcy) is an independent risk factor for atherosclerosis. Effective interventions to reduce HHcy-accelerated atherosclerosis are required.Objectives:This study aimed to investigate the effects of aerobic exercise (AE) and folate (FA) supplementation on plasma homocysteine (Hcy) level and atherosclerosis development in a mouse model.Methods:Six-week-old female apoE-/- mice were grouped into five groups (N = 6-8): HHcy (1.8 g/L DL-homocysteine (DL-Hcy) in drinking water), HHcy + AE (1.8 g/L DL-Hcy and aerobic exercise training on a treadmill), HHcy + FA (1.8 g/L DL-Hcy and 0.006% folate in diet), HHcy + AE + FA (1.8 g/L DL-Hcy, 0.006% folate, and aerobic exercise training on a treadmill), and a control group (regular water and diet). All treatment was sustained for 8 weeks. Triglyceride, cholesterol, lipoprotein, and Hcy levels were determined enzymatically. Plaque and monocyte chemoattractant protein-1 (MCP-1) expression levels in mouse aortic roots were evaluated by immunohistochemistry.Results:Compared to the HHcy group (18.88 ± 6.13 μmol/L), plasma Hcy concentration was significantly reduced in the HHcy + AE (14.79 ± 3.05 μmol/L, p = 0.04), HHcy + FA (9.4 ± 3.85 μmol/L, p < 0.001), and HHcy + AE + FA (9.33 ± 2.21 μmol/L, p < 0.001) groups. Significantly decreased aortic root plaque area and plaque burden were found in the HHcy + AE and HHcy + AE + FA groups compared to those in the HHcy group (both p < 0.05). Plasma MCP-1 level and MCP-1 expression in atherosclerotic lesions were significantly decreased in the HHcy + AE and HHcy + AE + FA groups compared to the HHcy group (all p < 0.05).Conclusions:AE reduced atherosclerosis development in HHcy apoE-/- mice independently of reducing Hcy levels. FA supplementation decreased plasma Hcy levels without attenuating HHcy-accelerated atherosclerosis. AE and FA supplementation have distinct mechanisms in benefiting atherosclerosis.

With the development of medical education, it has become a trend to implement integrated curriculum education for undergraduate students of clinical medicine. Peking University Health Science Center has been exploring the " new era" integrated curriculum in 2021. Aiming at the characteristics and objectives of integrated curriculum, the teaching team of cardiovascular system has initiated a new model for collective lesson preparation, which is characterized by independent disease modules, discussion on top-level design, curriculum structure and implementation of teaching of different chapters and stages. This paper proposed the procedure, effects and challenges from this new model of education and provide suggestions for optimizing the curriculum in future.

OBJECTIVE:To observe the multiple influence of cholesterol-lowering drug (simvastatin) on ankle brachial index (ABI), flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) of brachial artery blood vessel endothelium, and plasma level of monocyte chemotactic protein 1 (MCP-1) of hypercholesterolemia patients without coronary heart disease (CHD).METHODS:In the study, 51 patients with hypercholesterolemia application were treated with simvastatin (20 mg/d) therapy for 12 weeks. The metabolic index, ankle brachial index (ABI), FMD of brachial artery blood vessel endothelium detected by color doppler ultrasound instrument, the NMD of artery endothelial and the level of MCP 1 were measured before and after therapy respectively. All the results were analyzed and compared with another 30 cases of hypercholesterolemia patients selected without simvastatin treatment.RESULTS:After simvastatin therapy, the TC (total cholesterol) and LDL-C (low density lipoprotein cholesterin) levels were reduced apparently,the values decreased from the original (6.06 ± 1.03) mmol/L and (3.60 ± 0.82) mmol/L to (4.98 ± 1.34) mmol/L and (3.41 ± 0.10) mmol/L respectively (P<0.01, P< 0.05). Compared with no simvastatin treatment, the bilateral ABI levels were significantly elevated. The right side of ABI (ABIR) elevated from 1.11 ± 0.06 to 1.19 ± 0.07, and the left side of ABI (ABIL) also elevated from 1.12 ± 0.06 to 1.19 ± 0.10 (both sides were P<0.01). The FMD significantly increased from 7.75% ± 11.30% to 14.20% ± 15.39% (P < 0.05). The plasma levels of MCP-1 were apparently reduced from (112.0 ± 7.8) ng/L to (108.9 ± 6.2) ng/L (P < 0.05). All these items showed no obvious change within the control group.CONCLUSION:The API, FMD and plasma levels of MCP-1 of hypercholesterolemia patients without clear coronary heart disease can be improved by simvastatin treatment.

Background Many studies have shown that the serum uric acid (SUA) level is one of the cardiovascular risk factors. The aim of the study is to evaluate the relationship between SUA levels and the severity of coronary artery disease (CAD) assessed by angiography and the Syntax score in patients with obstructive CAD. Methods Participants who visited our hospital for a coronary angiography, from December 2007 to September 2012, were eligible for this analysis. SUA and other blood parameters after at least 12-hour fast were determined. First, the patients were divided into tertiles according to their Syntax scores (low Syntax score group: Syntax score ≤10.0; moderate Syntax score group: 10.0 18.0). Second, to clarify the association between SUA levels and major adverse cardiovascular events (MACEs), all patients were divided into two subgroups on the basis of SUA levels. The cutoff value of SUA was defined by diagnostic criteria of hyperuricemia. Patients were separated into normal SUA group (n=251, with SUA <416 ìmol/L for men and SUA <357 μmol/L for women) and high SUA group (n=96, with SUA <416 μmol/L for men and SUA ≥357 μmol/L for women). All participants were followed for a mean of 22.0 months (1–75 months, interquartile range: 28 months) for major adverse cardiovascular events (MACEs), including all-cause death, recurrent nonfatal myocardial infarction (re-MI) and recurrent percutaneous coronary intervention (re-PCI). Results A total of 347 patients were registered for the study. The SUA levels in the high Syntax score group were significantly higher than that of the moderate Syntax score group and the low Syntax score group ((392.3±81.6) μ/L vs. (329.9±71.0) μmol/L, P <0.001; (392.3±81.6) μmol/L vs. (311.4±64.7) μmol/L, P <0.001). The SUA level was positively correlated not only with the Syntax score (r=0.421, P <0.001; 95% CI: 0.333–0.512), but also with the number of diseased vessels (r=0.298, P <0.001; 95% CI: 0.194–0.396). After multiple linear regression analysis, SUA levels were identified to be independently correlated with a high Syntax score (B=0.033, 95% CI 0.023–0.042, P <0.001). Compared with the normal SUA subgroup, the high SUA subgroup tended to have a higher Syntax score (19.9±8.7 vs. 13.6±7.5, P <0.001) and more multi-vessel disease (70.8% vs. 46.6%, P <0.001). Follow-up data showed a higher incidence of MACE in the high SUA subgroup (20.8% vs. 6.0%, P <0.001). Binary Logistic regression analysis indicated that the elevated SUA can predict the long-term prognosis of patients with obstructive CAD (OR=2.968, 95% CI 1.256–7.011, P=0.013). Kaplan-Meier analysis showed a significantly lower event-free survival rate in patients with high SUA levels than in the normal SUA subgroup (79.2% vs. 94.0%, Log rank=17.645, P <0.001). Conclusions SUA levels were independently associated with the severity of CAD in patients with obstructive CAD. An elevated SUA is associated with cardiovascular events and may be useful as a biomarker of the severity of CAD.

目的 探讨辛伐他汀对无冠心病的高胆固醇血症患者超敏C反应蛋白(hs-CRP)和细胞间黏附分子-1(ICAM-1)含量的影响.方法 51例高胆固醇血症患者应用辛伐他汀20 mg/d,每晚顿服,治疗12周,分别在治疗前、治疗12周后测定患者的血脂指标、hs-CRP和ICAM-1.结果 辛伐他汀治疗后,患者总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)水平[(5.06±0.99)、(3.21±1.02) mmol/L]较治疗前[分别为(5.69±0.96)、(3.58±1.03)mmol/L]明显下降,差异均有统计学意义(P＜0.01,P＜0.05);与治疗前[hs-CRP、ICAM-1分别为(3.36±0.47)mg/L、(1.42±0.56)ng/ml]相比,治疗后,hs-CRP和ICAM-1水平[分别为(1.56±0.22)mg/L、(1.18±0.16)ng/ml]较治疗前明显降低,差异均有统计学意义(P＜0.05).结论 辛伐他汀可明显改善无冠心病的高胆固醇血症患者血浆hs-CRP和ICAM-1的含量.

BACKGROUND:As an adipocytokine, resistin has been proposed as a link between inflammation, metabolic disorder and atherosclerosis. The aim of the study is to evaluate whether serum resistin is associated with acute coronary syndrome (ACS) and major adverse cardiovascular events (MACEs) among postmenopausal women with ACS undergoing percutaneous coronary intervention (PCI). METHODS:A total of 106 consecutive postmenopausal women who underwent coronary angiography for evaluation of suspected myocardial ischemia were enrolled. Pre-procedure serum resistin, inflammatory and metabolic biomarkers were measured. All participants were followed for seven years for MACEs, including cardiovascular death, recurrent nonfatal myocardial infarction, and re-PCI. RESULTS:Patients with ACS (n = 69) had significantly higher resistin levels than those without coronary artery disease (CAD) (n = 37) (4.61 (1.79 - 10.80) ng/ml vs. 2.36 (0.85 - 4.15) ng/ml, P = 0.002). Correlation analysis revealed positive correlations between resistin levels and inflammatory and metabolic factors (P < 0.05). A follow-up of a mean of 83.4 months showed that patients with ACS suffered more MACEs than those without (13.0% vs. 2.7%, P = 0.05). Adjusted for cardiovascular risks, inflammatory and metabolic factors, multiple Logistic regression analysis indicated that an elevated resistin level was an independent predictor of ACS onset (OR = 1.139, 95%CI 1.024 - 1.268, P = 0.017) and of MACEs after PCI (OR = 1.099, 95%CI 1.015 - 1.189, P = 0.019). To clarify the association between resistin levels and MACEs, ACS patients were divided into two subgroups on the basis of resistin levels. Compared with the low resistin subgroup (≤ 4.35 ng/ml, n = 32), patients in the high resistin subgroup (> 4.35 ng/ml, n = 37) were more prone to suffer MACEs (21.6% vs. 3.1%, P = 0.015). Kaplan-Meier analysis showed a significantly lower event-free survival rate in ACS patients with high resistin levels than in the low resistin subgroup (78.4% vs. 96.9%, Log rank 5.594, P = 0.018). CONCLUSION:An elevated serum resistin level is associated with ACS and cardiovascular events and acts as a predictor in progression of ACS in postmenopausal women.

The glucagon-like peptide-1(GLP-1) receptor agonists exenatide and liraglutide are ideal drugs for treating diabetes mellitus.However,recent preclinical and clinical trial data suggest additional cardiovascular protective effects related to GLP-1 receptor agonists' therapy,including lowering blood pressure,improvements in left ventricular function and vascular endothelium function,protection of ischemia-injuried cardiac myocytes.Novel preclinical and clinical studies of GLP-1 receptor agonists on cardiovascular effects are outlined in this review.

OBJECTIVES:To evaluate the association of coronary artery endothelial function and plasma levels of low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) in patients with Type 2 Diabetes Mellitus (DM). METHODS:We investigated 90 participants from our institution between October 2007 to March 2010: non-DM (n = 60) and DM (n = 30). As an indicator of coronary endothelial dysfunction, we used non-invasive Doppler echocardiography to quantify coronary flow velocity reserve (CFVR) in the distal part of the left descending artery after rest and after intravenous adenosine administration. RESULTS:Plasma level of LDL-C was significantly higher in patients with DM than in non-DM (3.21 ± 0.64 vs. 2.86 ± 0.72 mmo/L, P < 0.05), but HDL-C level did not differ between the groups (1.01 ± 0.17 vs. 1.05 ± 0.19 mmo/L). Furthermore, the CFVR value was lower in DM patients than non-diabetics (2.45 ± 0.62 vs. 2.98 ± 0.68, P < 0.001). Plasma levels of LDL-C were negatively correlated with CFVR in all subjects (r = -0.35, P < 0.001; 95% confidence interval (CI): -0.52 - -0.15) and in the non-DM (r = -0.29, P < 0.05; 95% CI: -0.51- -0.05), with an even stronger negative correlation in the DM group (r = -0.42, P < 0.05; 95% CI: -0.68 - -0.06). Age (β = -0.019, s = 0.007, sβ = -0.435, 95% CI: -0.033 - -0.005, P = 0.008), LDL-C (β = -0.217, s = 0.105, sβ = -0.282, 95% CI: -0.428 - -0.005, P = 0.045) remained independently correlated with CFVR in the DM group. However, we found no correlation between HDL-C level and CFVR in any group. CONCLUSIONS:Diabetes may contribute to coronary artery disease (CAD) by inducing dysfunction of the coronary artery endothelium. Increased LDL-C level may adversely impair coronary endothelial function in DM. HDL-C may lose its endothelial-protective effects, in part as a result of pathological conditions, especially under abnormal glucose metabolism.

目的：通过对80岁以上老人进行运动心肺功能评估，观察进行有氧耐力训练和抗阻力训练的六个月后整体心肺功能和其他体检参数变化的特征，揭示高龄患者的有氧耐力训练的作用和意义。<br>　　方法：对38例动脉硬化、冠心病、高血压、糖尿病，年龄超过80岁的老人进行运动心肺功能测定，以及记录其他各项运动平衡功能参数。进行6个月的有氧耐力训练和抗阻训练。有氧耐力为慢跑与轻快走相结合，完成训练科目要求的里程和时间。耐力运动为Thera-Band弹力带训练，每周三次，每次一小时的抗阻训练。训练6个月再次运动心肺功能检测，并复查全身各项功能参数。

OBJECTIVE:Coronary flow velocity reserve (CFVR) is an important indicator of coronary endothelial functions and microcirculation. Pulse wave velocity (PWV) reflects the degree of aortic sclerosis and it is an independent predictor of cardiovascular events. The present study was designed to evaluate the correlation of large artery stiffness and CFVR.METHODS:A total of 101 consecutive subjects were enrolled to measure the brachial-ankle pulse wave velocity (baPWV). According to the presence or absence of higher baPWV (> 1400 cm/s), they were divided into 2 groups. Transthoracic echocardiography was employed to measure coronary flow velocity in coronary left anterior descending (LAD). Then after an intravenous infusion of adenosine triphosphate, the velocity of blood flow was measured when the vessel was in maximal dilation. The ratio of flow velocity of those in maximal dilation to those at rest was CFVR.RESULTS:The subjects with a higher baPWV (> 1400 cm/s) were markedly elder and had higher risks of hypertension and diabetes. Thus age, hypertension and diabetes contributed to arteriosclerosis. More importantly, the subjects with a higher baPWV (> 1400 cm/s) had a much lower level of CFVR (2.66 ± 0.74 vs 2.95 ± 0.76; P < 0.01) than those with a lower baPWV (< 1400 cm/s). Furthermore correlation analysis showed that CFVR and baPWV levels were significantly negatively correlated (r = -0.35, P < 0.01).CONCLUSIONS:A negative correlation exists between artery stiffness and coronary flow velocity reserve. The increased vascular stiffness may impair coronary endothelial function, cause the dysfunction of coronary microcirculation and raise the risks of cardiovascular events.

Aim To investigate whether aerobic exercise could decrease plasma homocysteine(Hcy) level and reduce atherosclerosis accelerated by hyperhomocysteinemia(HHcy) in ApoE-/-mice.Methods Six-week-old female ApoE-/-mice were assigned to three groups: control group,HHcy group and HHcy+exercise group.HHcy animal model was made by feeding a high Hcy chow.After 1 week of acclimatization,HHcy+exercise group was trained in a motorized rodent treadmill for 8 weeks(slope: 0°,speed: 15 m/min,60 min/d,5 d/wk).Plasma Hcy level and lipid levels were determined enzymatically by auto-biochemistry analysis system.Aortic roots were isolated for immunohistochemistry to compare the plaques' areas.Results Plasma Hcy levels in HHcy group were higher than control group,furthermore,the Hcy levels significantly decreased in HHcy+exercise group compared with HHcy group.There were not significant differences in body weight,daily drinking amount,plasma total cholesterol,LDLC,HDLC and triglyceride concentrations in the three groups.Compared with control group,atherosclerotic plaque area and plaque burden were increased in HHcy group.However,the plaque area and plaque burden in HHcy+exercise group were decreased when compared with HHcy group.Conclusion Aerobic exercise decreases plasma Hcy levels and reduces the development of atherosclerosis in HHcy ApoE-/ mice,which does not depend on the decrease of cholesterol levels.

INTRODUCTION:Fenofibrate, an agonist of peroxisome proliferator-activated receptor-α (PPAR-α), has a vascular protective effect.AIMS:We investigated the effect of the PPAR-α agonist on coronary artery endothelial function in patients with hypertriglyceridemia.METHODS:Fifty-eight patients with hypertriglyceridemia were divided into two groups: control (no treatment; n = 23) and fenofibrate treatment (n = 35), 200 mg/d, for 6 months. The patients had undergone rest and adenosine treatment to induce hyperemia for quantification of coronary flow velocity reserve (CFVR) by noninvasive Doppler echocardiography before treatment and at 6-month follow-up. Pulse wave velocity (PWV) was measured before treatment and at 6-month follow-up.RESULTS:CFVR was significantly improved with fenofibrate treatment as compared with baseline level and control group (3.14 ± 0.36 vs. 2.80 ± 0.58 and 2.79 ± 0.65, P < 0.01 and 0.05, respectively), with no difference between baseline levels and untreated controls. In addition, at 6 months, plasma level of homocysteine was significantly increased with fenofibrate treatment as compared with at baseline and control group (median 18.13 [range 14.46-22.02]μmol/L vs. 14.09 [12.01-18.81] and 13.34 [9.69-17.06]μmol/L, P < 0.001 and 0.01, respectively). Furthermore, at 6 months, PWV was significantly decreased with fenofibrate treatment as compared with control group (1446 ± 136 cm/s vs. 1570 ± 203 cm/s, P < 0.05).CONCLUSIONS:Treatment with PPAR-α agonist fenofibrate significantly improved CFVR and arterial stiffness in patients with hypertriglyceridemia. This endothelial protective effect may be reduced in part by the side effect of increasing homocysteine.

National occupational health standards-Diagnostic Criteria for Radiation Heart Injury has been approued and issued by Ministry of Health.On the basis of the extensive research literature,systematic study of the relevant laws and regulations in the criterias,further explicitly formulating the basis and principles of this criteria to guide the development of criteria.This criteria is mainly used for diagnosis of heart injury caused by radiation accident and medical radiation.To be better for using this criteria and to diagnosis correctly this disease and prompt treatment,the criteria-related content is interpreted in this article.

OBJECTIVE:To investigate the effects of advanced glycation end products (AGEs) on the secretion of monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) in vascular smooth muscle cells (VSMCs) and explore its possible intracellular signaling mechanism.METHODS:Primary rat VSMCs were isolated and identified. VSMCs were treated with glycation serum albumin (GSA), an important component of AGEs, in series of concentrations and time. The role of MAPK and NF-κB inhibitors was confirmed. The levels of MCP-1 and IL-8 were determined by enzyme-linked immunosorbent assay (ELISA).RESULTS:VSMCs were treated with GSA at the doses of 10 µg/ml, 100 µg/ml and 500 µg/ml respectively. In comparison with the control group, the levels of MCP-1 (13.01 ng/ml ± 0.12 ng/ml vs 7.02 ng/ml ± 0.26 ng/ml, P < 0.05) and IL-8 (12.6 ng/ml ± 0.86 ng/ml vs 3.07 ng/ml ± 0.35 ng/ml, P < 0.05) increased in the GSA-treated group, especially at the concentration of 100 µg/ml. After adjustment for cells proliferation, the levels of MCP-1 and IL-8 were still higher in the GSA-treated group. After a pretreatment of PDTC (10 µmol/L), SB203580 (5 µmol/L) and MG132 (10 µmol/L), the levels of MCP-1 and IL-8 decreased. However, it had no change when pretreated with PD98059 (20 µmol/L).CONCLUSION:GSA promotes the secretion of MCP-1 and IL-8 in VSMCs. Such an effect is not dependent on cellular proliferation. It may be realized through an activation of NF-κB by p38MAPK-sensitive intracellular signaling pathway.

Rad is a member of a subclass of small GTP-binding proteins, the RGK family. In the present study we investigated the role of Rad protein in regulating cardiomyocyte viability. DNA fragmentation and TUNEL assays demonstrated that Rad promoted rat neonatal cardiomyocyte apoptosis. Rad silencing fully blocked serum deprivation induced apoptosis, indicating Rad is necessary for trigger cardiomyocyte apoptosis. Rad overexpression caused a dramatic decrease of the anti-apoptotic molecule Bcl-x(L), whereas Bcl-x(L) overexpression protected cardiomyocytes against Rad-induced apoptosis. Rad-triggered apoptosis was mediated by the activation of p38 MAPK. The p38 blocker SB203580 effectively protected cardiomyocytes against Rad-evoked apoptosis.

Objective To investigate whether coronary artery endothelial function was damaged in patients with chronic hyperhomocysteinemia(HHcy) and if so,whether this impaired endothelial function is induced by the uncoupling of endothelial nitric oxide synthase(eNOS).Methods The 71 subjects were divided into 2 groups,control(n=50) and HHcy(n=21).CFVR was measured by noninvasive Doppler echocardiography.Plasma levels of tetrahydrobiopterin(BH4) and nitric oxide(NO) were measured by high-performance liquid chromatography and ELISA kits,respectively.Results Plasma levels of NO and BH4 were significantly lower in patients with HHcy than in controls(P0.05).CFVR was markedly reduced in the HHcy group than control group(P0.05).In addition,plasma level of homocysteine was negatively correlated with NO and CFVR.Conclusion Our results showed that chronic HHcy may contribute to coronary artery disease by inducing dysfunction of the coronary artery endothelium through uncoupling of eNOS.

Objective To evaluate the impact of hyperglycemia on left ventricular diastolic function in the patients with coronary heart disease(CHD) after stent implanatation.Methods A total of 126 CAD patients with diabetes mellitus were collected after stent implantation,who were classified by HbA1c,Left ventricular diastolic function of CAD patients with hyperglycemia(group A) had been compared with that of normal blood sugar under control group(group B).The mitral inflow profile(E,A,E/A) and the deceleration time(DT) were measured,the early-diastolic(Em) peak velocities of the septal mitral annulus was measured by the Dopper tissue image(TDI).Results In group A,DT decreased significantly after three months and six months.Em and the value of E/A ratio changed significantly within twenty hours,three months and six months(P0.01).In group B,DT showed significant differences after six months(P0.05).The value of E/A ratio improved after three months and six months of stent implatation,but did not change between three and six months.Em did not improved significantly.Conclusions Left ventricular diastolic function did not improve in those patients with poor blood sugar control long-term after stent implantation.The importance of hyperglycemia control in patients with CAD should be laid emphasis on.

Hyperhomocysteinemia (HHcy) has been associated with impaired vascular endothelial function. Our previous study demonstrated significantly higher secretion of the chemokine monocyte chemoattractant protein-1 from monocytes in response to lipopolysaccharide in patients with HHcy. In the present study, we investigated whether coronary endothelial function was damaged in patients with chronic HHcy (plasma level of homocysteine >15 μmol/l) and, if so, whether this impaired endothelial function is induced by the uncoupling of endothelial nitric oxide synthase (eNOS). When tetrahydrobiopterin levels are inadequate, eNOS is no longer coupled to l-arginine oxidation, which results in reactive oxygen species rather than nitric oxide production, thereby inducing vascular endothelial dysfunction. The 71 participants were divided into two groups, control ( n = 50) and HHcy ( n = 21). Quantification of coronary flow velocity reserve (CFVR) was after rest and after adenosine administration done by noninvasive Doppler echocardiography. Plasma levels of nitric oxide and tetrahydrobiopterin were significantly lower in patients with HHcy than in controls (99.54 ± 32.23 vs. 119.50 ± 37.68 μmol/l and 1.43 ± 0.46 vs. 1.73 ± 0.56 pmol/ml, all P < 0.05). Furthermore, CFVR was significantly lower in the HHcy than the control group (2.76 ± 0.49 vs. 3.09 ± 0.52, P < 0.05). In addition, plasma level of homocysteine was negatively correlated with CFVR. Chronic HHcy may contribute to coronary artery disease by inducing dysfunction of the coronary artery endothelium. The uncoupling of eNOS induced by HHcy in patients with chronic HHcy may explain this adverse effect in part.