IDOL G51S Variant Is Associated With High Blood Cholesterol and Increases Low-Density Lipoprotein Receptor Degradation.

OBJECTIVE: A high level of LDL-C (low-density lipoprotein cholesterol) is a major risk factor for cardiovascular disease. The E3 ubiquitin ligase named IDOL (inducible degrader of the LDLR [LDL receptor]; also known as MYLIP [myosin regulatory light chain interacting protein]) mediates degradation of LDLR through ubiquitinating its C-terminal tail. But the expression profile of IDOL differs greatly in the livers of mice and humans. Whether IDOL is able to regulate LDL-C levels in humans remains to be determined. Approach and Results: By using whole-exome sequencing, we identified a nonsynonymous variant rs149696224 in the IDOL gene that causes a G51S (Gly-to-Ser substitution at the amino acid site 51) from a Chinese Uygur family. Large cohort analysis revealed IDOL G51S carriers (+/G51S) displayed significantly higher LDL-C levels. Mechanistically, the G51S mutation stabilized IDOL protein by inhibiting its dimerization and preventing self-ubiquitination and subsequent proteasomal degradation. IDOL(G51S) exhibited a stronger ability to promote ubiquitination and degradation of LDLR. Adeno-associated virus-mediated expression of IDOL(G51S) in mouse liver decreased hepatic LDLR and increased serum levels of LDL-C, total cholesterol, and triglyceride. CONCLUSIONS: Our study demonstrates that IDOL(G51S) is a gain-of-function variant responsible for high LDL-C in both humans and mice. These results suggest that IDOL is a key player regulating cholesterol level in humans.

Changes on Stroke Burden Attributable to Ambient Fine Particulate Matter in China.

Objective: In recent decades, China has implemented a series of policies to address air pollution. We aimed to assess the health effects of these policies on stroke burden attributable to ambient fine particulate matter (PM 2.5). Methods: Joinpoint regression was applied to explore the temporal tendency of stroke burden based on data from the Global Burden of Disease 2019 study. Results: The age-standardized rates of disability-adjusted life year (DALY) for stroke attributable to ambient PM 2.5 in China, increased dramatically during 1990-2012, subsequently decreased at an annual percentage change (APC) of -1.98 [95% confidence interval ( CI): -2.26, -1.71] during 2012-2019. For ischemic stroke (IS), the age-standardized DALY rates doubled from 1990 to 2014, and decreased at an APC of -0.83 (95% CI: -1.33, -0.33) during 2014-2019. Intracerebral hemorrhage (ICH) showed a substantial increase in age-standardized DALY rates from 1990 to 2003, followed by declining trends, with APCs of -1.46 (95% CI: -2.74, -0.16) during 2003-2007 and -3.33 (95% CI: -3.61, -3.06) during 2011-2019, respectively. Conversely, the age-standardized DALY rates for subarachnoid hemorrhage (SAH) generally declined during 1990-2019. Conclusion: Our results clarified the dynamic changes of the ambient PM 2.5-attributable stroke burden in China during 1990-2019, highlighting the health effects of air quality improvement policies.

Life's essential 8 and risk of subclinical atherosclerosis progression: a prospective cohort study.

BACKGROUND: Previous studies have demonstrated the benefits of ideal cardiovascular health (CVH) in reducing cardiovascular risk. However, its role in subclinical atherosclerosis (SA) progression remains unclear. We aim to examine the association of CVH, estimated by the American Heart Association's new Life's Essential 8 (LE8), with the progression of SA. METHODS: This prospective cohort study was conducted among 972 asymptomatic Chinese participants and followed up for 5.7 years. The LE8 score (range, 0-100) consisted of blood pressure, lipids, glucose, body mass index, smoking status, diet health, physical activity and sleep health was evaluated in 1998 and 2008-2009. Progression of SA was determined by carotid plaque and coronary artery calcification (CAC) in 2008-2009 and 2013-2014. Log-binomial regression model was used to estimate the association of LE8 score with SA progression. RESULTS: Each 10 points increment in LE8 score was associated with 15.2% (RR: 0.848, 95% CI: 0.797-0.902), 17.7% (RR: 0.823, 95% CI: 0.766-0.884) and 12.0% (RR: 0.880, 95% CI: 0.845-0.916) lower risks of carotid plaque, CAC and overall SA progression, respectively. Compared with participants with non-ideal CVH at both visits, the participants with ideal CVH at both visits had 39.1% (RR: 0.609, 95% CI: 0.494-0.752), 41.0% (RR: 0.590, 95% CI: 0.456-0.764) and 29.7% (RR: 0.703, 95% CI: 0.598-0.825) lower risks of carotid plaque, CAC and overall SA progression, respectively. CONCLUSIONS: Higher LE8 scores were associated with lower risks of SA progression. Besides, long-term maintenance of optimal CVH was more beneficial to prevent SA progression.

Association between Fruit and Vegetable Intake and Arterial Stiffness: The China-PAR Project.

Objective: This study aimed to investigate the association between fruit and vegetable intake and arterial stiffness. Methods: We conducted a cohort-based study comprising 6,628 participants with arterial stiffness information in the Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) project. A semi-quantitative food-frequency questionnaire was used to assess baseline (2007-2008) and recent (2018-2021) fruit and vegetable intake. We assessed changes in fruit and vegetable intake from 2007-2008 to 2018-2021 in 6,481 participants. Arterial stiffness was measured using the arterial velocity-pulse index (AVI) and arterial pressure-volume index (API). Elevated AVI and API values were defined according to diverse age reference ranges. Results: Multivariable-adjusted linear regression models revealed that every 100 g/d increment in fruit and vegetable intake was associated with a 0.11 decrease in AVI ( B= -0.11; 95% confidence interval [ CI]: -0.20, -0.02) on average, rather than API ( B = 0.02; 95% CI: -0.09, 0.13). The risk of elevated AVI (odds ratio [ OR] = 0.82; 95% CI: 0.70, 0.97) is 18% lower in individuals with high intake (≥ 500 g/d) than in those with low intake (< 500 g/d). Furthermore, maintaining a high intake in the past median of 11.5 years of follow-up was associated with an even lower risk of elevated AVI compared with a low intake at both baseline and follow-up ( OR = 0.64; 95% CI: 0.49, 0.83). Conclusion: Fruit and vegetable intake was negatively associated with arterial stiffness, emphasizing recommendations for adherence to fruit and vegetable intake for the prevention of arterial stiffness.

Lifestyle improvement and the reduced risk of cardiovascular disease: the China-PAR project.

BACKGROUND: The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease (CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project (Prediction for Atherosclerotic Cardiovascular Disease Risk in China). METHODS: A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors (LFs) (smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The risk advancement periods (RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage (PAR%) were also calculated. RESULTS: A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1 healthy LFs, maintaining 3-4 healthy LFs was associated with a 40% risk reduction of incident CVD (HR = 0.60, 95% CI: 0.45-0.79) and delayed CVD risk by 6.31 years (RAP: -6.31 [-9.92, -2.70] years). The PAR% of maintaining 3-4 unhealthy LFs was 22.0% compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2 to 3-4 was associated with a 23% lower risk of CVD (HR = 0.77, 95% CI: 0.60-0.98). CONCLUSIONS: Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.

Association of Estimated Pulse Wave Velocity and the Dynamic Changes in Estimated Pulse Wave Velocity with All-Cause Mortality among Middle-Aged and Elderly Chinese.

Objective: We aimed to clarify the association between estimated pulse wave velocity (ePWV) and the changes in ePWV with all-cause mortality among middle-aged and elderly Chinese. Methods: Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS) from 2011-2018. The ePWV was calculated using an equation that included age and mean blood pressure (MBP). The ΔePWV was assessed as the difference in ePWV between the first two waves. Cox proportional hazard models were used to determine the association between ePWV and ΔePWV with all-cause mortality after adjustment for potential confounders. Results: Of 13,116 participants during a median follow-up of 7.0 years, 1,356 deaths occurred. An increased ePWV was independently associated with all-cause mortality. The hazard ratio [95% confidence interval ( CI)] for participants from the 1 st-4 th quartile groups was 1.00, 1.69 (1.31-2.18), 3.09 (2.44-3.91), and 8.54 (6.78-10.75), respectively. Each standard deviation (SD) increment of ePWV increased the risk of all-cause mortality by 132%. Furthermore, the ΔePWV was significantly associated with a 1.28-fold (95% CI, 1.18-1.38) risk of all-cause mortality per SD increment. Conclusion: This cohort study provided novel evidence from a Chinese population that an increased ePWV or progression of the ePWV was independently associated with all-cause mortality, which highlighted the importance of mitigating ePWV progression in clinical practice.

Associations of tea consumption with blood pressure progression and hypertension incidence.

BACKGROUND: Association between tea consumption and incident hypertension remains uncertain. This study conducted to examine the health effects of tea consumption on blood pressure progression and hypertension incidence. METHODS: A population-based cohort of 38,913 Chinese participants without hypertension at baseline were included in the current study. Information on tea consumption was collected through standardized questionnaires. Associations of tea consumption with blood pressure progression and incident hypertension were analyzed using logistic regression models and Cox proportional hazards regression models, respectively. RESULTS: During a median follow-up of 5.9 years, 17,657 individuals had experienced progression to a higher blood pressure stage and 5,935 individuals had developed hypertension. In multivariate analyses, habitual tea drinkers (≥ 3 times/week for at least six months) had a 17% lower risk for blood pressure progression [odds ratio (OR) = 0.83, 95% CI: 0.79-0.88] and a 14% decreased risk for incident hypertension [hazard ratio (HR) = 0.86, 95% CI: 0.80-0.91] compared with non-habitual tea drinkers. Individuals in different baseline blood pressure groups could obtain similar benefit from habitual tea drinking. In terms of tea consumption amount, an inverse, linear dose-response relation between monthly consumption of tea leaves and risk of blood pressure progression was observed, while the risk of incident hypertension did not reduce further after consuming around 100 g of tea leaves per month. CONCLUSIONS: Our study demonstrated that habitual tea consumption could provide preventive effect against blood pressure progression and hypertension incidence.

Effects of the total physical activity and its changes on incidence, progression, and remission of hypertension.

OBJECTIVES: Moderate to vigorous physical activity is recommended to prevent hypertension according to the current guidelines. However, the degree to which the total physical activity (TPA) and its changes benefit normotensives and hypertensives is uncertain. We aimed to examine the effects of TPA and its changes on the incidence, progression, and remission of hypertension in the large-scale prospective cohorts. METHODS: A total of 73,077 participants (55,101 normotensives and 17,976 hypertensives) were eligible for TPA analyses. During a mean follow-up of 7.16 years (394,038 person-years), 12,211 hypertension cases were identified. TPA was estimated as metabolic equivalents and categorized into quartiles. Cox proportional hazards regression and multivariable logistic regression were used to estimate associations of TPA and changes in TPA with incident hypertension and progression/remission of hypertension. RESULTS: Compared with the lowest quartile of TPA, normotensives at the third and the highest quartile had a decreased risk of incident hypertension, with hazard ratios (HRs) of 0.86 [95% confidence interval (CI): 0.81-0.91] and 0.81 (95% CI: 0.77-0.86), respectively. Hypertensives at the highest quartile of TPA demonstrated a decreased risk of progression of hypertension [odds ratio (OR) = 0.87, 95% CI: 0.79-0.95], and an increased probability of hypertension remission (OR = 1.17, 95% CI: 1.05-1.29). Moreover, getting active from a sedentary lifestyle during the follow-up period could reduce 25% (HR = 0.75, 95% CI: 0.58-0.96) risk of incident hypertension, whereas those becoming sedentary did not achieve benefit from initially being active. CONCLUSIONS: Our findings indicated that increasing and maintaining TPA levels could benefit normotensives, whereas higher TPA levels were needed to effectively control progression and improve remission of hypertension. Physical activity played undoubtedly an essential role in both primary and secondary prevention of hypertension.

The effect of total cholesterol on myocardial infarction in Chinese male hypertension population.

OBJECTIVE: Total cholesterol (TC) is an important risk factor for myocardial infarction (MI), but the effect of TC on MI in Chinese male hypertension population has not been well documented. We conducted a prospective cohort study to determine the incidence and relative risk for MI across a wide range of TC levels in Chinese male hypertension population. METHODS: A cohort of 5298 male employees aged 18-74 years recruited from Capital Steel and Iron Company in Beijing of China in 1974-1980 was followed up for an average of 20.84 years. A total of 122 incident MI cases were identified during the period of follow-up. RESULTS: The incidence of MI among participants with elevated TC and those with desirable TC in male non-hypertension population was 137.20 and 63.81 per 100,000 person-years, respectively; and the corresponding incidence in male hypertension population was 279.80 and 130.96 per 100,000 person-years, respectively. After adjustment for important covariables, 10.38%, 16.71%, and 23.80% of MI cases were attributable to hypertension, elevated TC, and hypertension plus elevated TC, respectively. In male hypertension population, the multivariate adjusted hazard ratios of MI were 1.21, 2.39, 3.38, and 3.95 for participants with TC level of 5.17-5.68, 5.69-6.20, 6.21-6.71, and > or = 6.72 mmol/L, compared with those with TC < 5.17 mmol/L. The corresponding population attributable risks were 2.92%, 9.20%, 8.87%, and 9.84%, respectively. CONCLUSION: Elevated TC is an important independent risk factor of MI both in male non-hypertension and hypertension populations. There is a linear association between TC level and MI incidence in Chinese male hypertension population.

[Advances in genome-wide association study of coronary heart disease].

As a new effective strategy for researching complex diseases, genome-wide association study (GWAS) has being developed rapidly in recent years worldwide. The world genomic study has been taken into a new stage, since a series of disease related genes or variants have been identified by GWAS strategy. Coronary heart disease (CHD) is a complex disease that is caused by both environmental and genetic factors, and has become one of the leading causes of death and disability worldwide. With the application of GWAS strategy, researchers from all over the world have identified many susceptibility loci or regions of CHD that were unable to be identified by candidate gene case-control study. The present paper reviewed the important progresses worldwide attained in GWAS of CHD in recent years. Then it is also expounded the challenges we are facing nowadays in GWAS as well as the future study direction. The information outlined in this paper provides us a valuable guidance upon further exploration into genetic mechanism of CHD.

Associations of soybean products intake with blood pressure changes and hypertension incidence: the China-PAR project.

BACKGROUND: The relationships between dietary intake of soybean products and incident hypertension were still uncertain. This study aimed to illustrate the associations between intake of soybean products with risks of incident hypertension and longitudinal changes of blood pressure in a prospective cohort study. METHODS: We included 67, 499 general Chinese adults from the Project of Prediction for Atherosclerosis Cardiovascular Disease Risk in China (China-PAR). Information about soybean products consumption was collected by standardized questionnaires, and study participants were categorized into the ideal (≥ 125 g/day) or non-ideal (< 125 g/day) group. Hazard ratios (HRs) and corresponding 95% confidence intervals (95% CIs) for incident hypertension were calculated using Cox proportional hazard models. Among participants with repeated measures of blood pressure, generalized linear models were used to examine the relationships between soybean products consumption and blood pressure changes. RESULTS: During a median follow-up of 7.4 years, compared with participants who consumed < 125 g of soybean products per day, multivariable adjusted HR for those in the ideal group was 0.73 (0.67-0.80). This inverse association remained robust across most subgroups while significant interactions were tested between soybean products intake and age, sex, urbanization and geographic region (P values for interaction < 0.05). The mean systolic and diastolic blood pressure levels were 1.05 (0.71-1.39) mmHg and 0.44 (0.22-0.66) mmHg lower among participants in the ideal group than those in the non-ideal group. CONCLUSIONS: Our study showed that intake of soybean products might reduce the long-term blood pressure levels and hypertension incidence among Chinese population, which has important public health implications for primary prevention of hypertension.

Association of cardiovascular diseases with milk intake among general Chinese adults.

BACKGROUND: The association of milk intake with cardiovascular disease (CVD) and cause-specific mortality remained controversial and evidence among the Chinese population was limited. We aimed to study the relationship between milk intake and CVDs among general Chinese adults. METHODS: A total of 104,957 participants received questionnaire survey. Results of physical examination such as anthropometric measurements and biochemical tests during 2007 to 2008, demographic data and their information on milk intake were collected through standardized questionnaires. Cox proportional hazard regression models were used to calculate hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) of CVD incidence, cause-specific mortality and all-cause mortality related to milk intake. Restricted cubic splines (RCSs) were applied to examine dose-response associations. RESULTS: Among the 91,757 participants with a median follow-up period of 5.8 years, we documented 3877 CVD cases and 4091 all-cause deaths. Compared with participants who never consumed milk, the multivariate-adjusted HRs (95% CIs) of CVD incidence for 1 to 150 g/day, 151 to 299 g/day, and ≥300 g/day were 0.94 (0.86-1.03) (P > 0.05), 0.77 (0.66-0.89) (P < 0.05), and 0.59 (0.40-0.89) (P < 0.05), respectively; each 100 g increase of daily milk intake was associated with 11% lower risk of CVD incidence (HR, 0.89; 95% CI: 0.85-0.94; P < 0.001), and 11% lower risk of CVD mortality (HR, 0.89; 95% CI: 0.82-0.97; P = 0.008) after adjustment for age, sex, residential area, geographic region, education level, family history of CVD, smoking, alcohol drinking, physical activity level, body mass index, and healthy diet status (ideal or not). RCS analyses also showed a linear dose-response relationship with CVD (P for overall significance of the curve <0.001; P for non-linearity = 0.979; P for linearity <0.001) and stroke (P for overall significance of the curve = 0.010; P for non-linearity = 0.998; P for linearity = 0.002) incidence, and CVD mortality (P for overall significance of the curve = 0.045; P for non-linearity = 0.768; P for linearity = 0.014) within the current range of daily milk intake. CONCLUSIONS: Daily milk intake was associated with lower risk of CVD incidence and mortality in a linear inverse relationship. The findings provide new evidence for dietary recommendations in CVD prevention among Chinese adults and people with similar dietary pattern in other countries.

Beneficial effects of moderate to vigorous physical activity on cardiovascular disease among Chinese adults.

BACKGROUND: In China, lack of evidence remains a significant challenge for the national initiative to promote physical activity (PA). We aimed to quantify the beneficial effects of meeting or maintaining the recommended PA level [150 minutes per week (min/wk) of moderate PA or 75 min/wk of vigorous PA or an equivalent combination] on incident cardiovascular disease (CVD) among Chinese population. METHODS: We included 100,560 participants without history of CVD from three cohorts in the Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) project. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD events and its subtypes, including stroke, coronary heart disease, heart failure, and CVD death. RESULTS: During a median follow-up of 7.3 years (range: 6-15 years), 777,163 person-years and 4693 incident CVD events were observed. Compared with participants who were inactive at baseline, the multivariable adjusted HR (95% CI) of developing CVD was 0.74 (0.69-0.79) for those who met recommended moderate to vigorous physical activity (MVPA) level at baseline. Furthermore, the risk of CVD incidence was reduced with increment of MVPA (P trend < 0.001), and the HR (95% CI) of highly-active versus inactive category was 0.62 (0.56-0.68). Compared with individuals who were inactive both at the baseline and follow-up, those keeping active over the period of follow-up had a substantial lower risk of incident CVD with the HR (95% CI) of 0.57 (0.43-0.77). CONCLUSIONS: The findings demonstrated that meeting and maintaining the recommended MVPA level could reduce the cardiovascular risk. Wider adoption of the PA recommendations would have considerable health impacts to the Chinese population.

[Body mass index and prognosis in patients with systolic heart failure].

OBJECTIVE: In individuals without cardiovascular disease, elevated body mass index (BMI) is associated with an increased risk of death. However, in patients with certain chronic diseases, including heart failure, low BMI has been associated with increased mortality. We investigated the association between BMI and prognosis in patients with systolic HF. METHOD: Follow-up was made on 540 patients (mean age 58.53 years, 84.2% men) with systolic HF (LVEF < or = 45%) and association between BMI and adverse cardiac events was analyzed. RESULTS: During a median follow-up of 24 months, 92 patients died including 87 cases of cardiac death and 92 patients were rehospitalized. Compared with patients with BMI higher than 28.0 kg/m(2), patients in lower BMI categories (BMI < or = 18.5 kg/m(2) and > or = 18.5 kg/m(2) < 24.0 kg/m(2)) had a graded increase in the all cause death rate [5.44 (1.78 - 16.66), 4.30 (1.71 - 10.82)], cardiac death rate [OR(95%CI): 5.42 (1.77 - 16.59), 4.00 (1.59 - 10.10)], HF death rate [8.94 (2.37 - 33.74), 4.97 (1.52 - 16.20)] and MACE rate [2.10 (1.09 - 4.07), 1.79 (1.14 - 2.82)]. After adjustment for age, gender, LVEF and NYHA grade using cox regression analysis, BMI categories still significantly associated with all cause death rate (OR = 0.77, P < 0.05), cardiac death rate (OR = 0.78, P < 0.05) and HF death rate (OR = 0.79, P < 0.05). CONCLUSION: In patients with systolic heart failure, lower BMI was an independent predictor of increased all cause death rate, cardiac death rate and HF death rate.

Transplantation efficacy of autologous bone marrow mesenchymal stem cells combined with atorvastatin for acute myocardial infarction (TEAM-AMI): rationale and design of a randomized, double-blind, placebo-controlled, multi-center, Phase II TEAM-AMI trial.

Aim: To determine the efficacy and safety of intracoronary infusion of autologous bone marrow mesenchymal stem cells (MSCINJ) in combination with intensive atorvastatin (ATV) treatment for patients with anterior ST-segment elevation myocardial infarction-elevation myocardial infarction. Patients & methods: The trial enrolls a total of 100 patients with anterior ST-elevation myocardial infarction. The subjects are randomly assigned (1:1:1:1) to receive routine ATV (20 mg/d) with placebo or MSCsINJ and intensive ATV (80 mg/d) with placebo or MSCsINJ. The primary end point is the absolute change of left ventricular ejection fraction within 12 months. The secondary end points include parameters in cardiac function, remodeling and regeneration, quality of life, biomarkers and clinical outcomes. Results & conclusion: The trial will implicate the essential of cardiac micro-environment improvement ('fertilizing') for cell-based therapy. Clinical Trial Registration: NCT03047772.

Influence of fibrinogen beta-chain gene variations on risk of myocardial infarction in a Chinese Han population.

BACKGROUND: Although the role of fibrinogen as a predictor of acute myocardial infarction (MI) has been well-established, the association of genetic polymorphisms in the fibrinogen gene with MI is still controversial. This study was conducted to elucidate the association between the genetic polymorphisms of the fibrinogen beta-chain (FGB) gene and MI in Chinese Han population. METHODS: The occurrence of 3 common polymorphisms (i.e., -455G/A, R448K and 8558C/G) in a case-control study including 508 patients with MI and 503 healthy controls was investigated. Results Analyses of single polymorphisms showed that individuals carrying the rare alleles for the 3 polymorphisms were significantly associated with a decreased risk of MI. Logistic regression analysis indicated that R448K remained independently associated with MI after adjustment for environmental risk factors (adjusted odds ratio(OR) = 0.71 for KK/RK versus RR, P = 0.023). The three polymorphisms were found to be in strong linkage disequilibrium. Haplotype analyses showed that the A-K-G haplotype (-455A, 448K, 8558G) was associated with a protective effect against MI. Compared with the common haplotype G-R-C, the adjusted OR for A-K-G was 0.68 (95% CI, 0.51-0.90; P = 0.006). CONCLUSION: These data indicate that individuals carrying the FGB 448K allele may be protective against having MI in this population.

Relationship between cystathionine gamma-lyase gene polymorphism and essential hypertension in Northern Chinese Han population.

BACKGROUND: Hydrogen sulfide (H(2)S) plays an important role in the smooth muscle cell relaxation and thereby participates in the development of hypertension. Cystathionine gamma-lyase is the key enzyme in the endogenous production of H(2)S. Up to now, the reports on the relationship between the polymorphisms of cystathionine gamma-lyase gene (CTH) and essential hypertension (EH) are limited. This study was designed to assess their underlying relationship. METHODS: A total of 503 hypertensive patients and 490 age-, gender- and area-matched normotensive controls were enrolled in this study. Based on the FASTSNP, a web server to identify putative functional single nucleotide polymorphisms (SNPs) of genes, we selected two SNPs, rs482843 and rs1021737, in the CTH gene for genotyping. Genotyping was performed by the polymerase chain reaction and restriction fragment length polymorphism method (PCR-RFLP). The frequencies of the alleles and genotypes between cases and controls were compared by the chi-square test. The program Haplo. stats was used to investigate the relationship between the haplotypes and EH. RESULTS: These two SNPs were in Hardy-Weinberg Equilibrium in both cases and controls. The genotype distribution and allele frequencies of them did not significantly differ between cases and controls (all P > 0.05). In the stepwise logistic regression analysis we failed to observe their association with hypertension. In addition, none of the four estimated haplotypes or diplotypes significantly increased or decreased the risk of hypertension before or after adjustment for several known risk factors. CONCLUSIONS: The present study suggests that the SNPs rs482843 and rs1021737 of the CTH gene were not associated with essential hypertension in the Northern Chinese Han population. However, replications in other populations and further functional studies are still necessary to clarify the role of the CTH gene in the pathogenesis of EH.

[Association between single nucleotide polymorphisms of matrix metalloproteinase-3 gene and the severity of coronary atherosclerosis in patients with coronary artery disease].

OBJECTIVE: To investigate the association between the severity of coronary arteries in patients with coronary artery disease and the single nucleotide polymorphisms of MMP-3 gene. METHODS: One thousand and three hundred seventy-one patients with coronary artery disease (CAD) diagnosed by coronary angiography and six hundred and ninety-five healthy controls without CAD were enrolled in this study. The SNPs of -1612 5A/6A, -376C/G, Glu45Lys of MMP-3 were genotyped by restriction fragment length polymorphism analysis (RFLP) in all subjects. Univariate analysis was applied to measure the association of the single nucleotide polymorphisms with the severity of coronary arteries. RESULTS: The minor allele frequency of -1612 5A/6A was 0.189, 0.185, 0.183 and 0.152 (P < 0.05 vs. non-CAD control and single stenosis), the minor allele frequency of -376C/G was 0.311, 0.329, 0.326 and 0.325, and the minor allele frequency of Glu45Lys was 0.367, 0.423, 0.417 and 0.405 in non-CAD control, CAD patients with single, two and three vessels stenosis, respectively. 5A allele frequency is significant lower in the group with three vessels stenosis than in non-CAD control and CAD patients with single vessel stenosis (OR = 0.74, P = 0.04). The 5A/5A and 5A/6A genotypes frequency is significant lower in the group with three vessels stenosis than in the non-CAD group and CAD patients with single vessel stenosis (OR = 0.74, P = 0.04). CONCLUSIONS: The single nucleotide polymorphism of -1612 5A/6A of MMP-3 gene may be associated with the severity of coronary atherosclerosis in the Chinese Han patients with coronary artery disease, and the 5A allele might therefore, play a protective role on the progression of coronary atherosclerosis.

[A rat model of pulmonary fibrosis induced by infusing bleomycin quickly through tracheal intubation].

OBJECTIVE: To study the approach for developing a rat model of pulmonary fibrosis induced by bleomycin (BLM). METHOD: Different doses (7, 6, 5, 3.4, 2, 1 mg/kg) of bleomycin A5-saline were infused into the rats' lung in bleomycin-treated group through tracheal intubation, and rats in sham-operated group were infused with same volume of saline. The living state and lung pathology of the rats were observed. The author deeply studied the condition of the rats in 1 mg/kg bleomycin-treated group, and the changes of body weight and lung pathology were observed. Lung quotient, the content of transforming growth factor beta1(TGF-beta1) and platelet-derived growth factor (PDGF) in serum were measured on the 14th, 28th and 45th day of the experiment. RESULTS: The study demonstrated that infusing large doses of bleomycin A5 quickly through tracheal intubation had a high mortality, and infusing 1 mg/kg quickly could successfully develop an animal model of pulmonary fibrosis. Compared with the sham-operated group, fibrosis was appeared obviously in the rats' lung in 1 mg/kg bleomycin A5-treated group after 14 days of experiment, diffuse fibrosis was appeared after 28 days of experiment, and the fibrosis became more severe after 45 days of experiment. The body weight of the rats in bleomycin-treated group was declined after 3, 7 and 14 days of experiment as compared with the sham-operated group (P<0.01). Twenty-one days after the experiment, the body weight was declined too, but there was no significant difference between the bleomycin-treated group and the sham-operated group (P>0.05). Lung quotient was increased 14, 28 and 45 days after the experiment (P<0.01), the level of serum TGF-beta1 began to increase since 28 days after the experiment (P<0.05, P<0.01), and the level of serum PDGF also increased gradually 45 days after the experiment (P<0.05). And the mortality rate of 1 mg/kg bleomycin A5-treated group was lower than those of the other doses of bleomycin A5-treated groups. CONCLUSION: A rat model of pulmonary fibrosis can be duplicated successfully by infusing 1 mg/kg bleomycin A5 quickly through tracheal intubation.

[Influence of Feixian Formula on serum transforming growth factor-beta1 and platelet-derived growth factor in rats with bleomycin-induced pulmonary fibrosis].

OBJECTIVE: To observe the effects of Feixian Formula, a compound traditional Chinese herbal medicine for treating pulmonary fibrosis, on bleomycin-induced pulmonary fibrosis in rats, and its influence on serum transforming growth factor-beta1 (TGF-beta1) and platelet-derived growth factor (PDGF). METHODS: Seventy-two male Wistar rats were infused with bleomycin (1 mg/kg) through tracheal intubation to induce pulmonary fibrosis, and they were randomly divided into untreated group (n=24), prednisone-treated group (n=24) and Feixian Formula-treated group (n=24). Fifteen male Wistar rats of the sham-operated group were infused with equivalent normal saline. Twenty-four hours after operation, prednisone (5 mg/kg) and Feixian Formula (1.25 g/kg) were given to the prednisone-treated group and Feixian Formula-treated group respectively by intragastric administration once a day. Equivalent saline was administered to rats of the untreated group and sham-operated group. On the 14th, 28th and 45th day, 5 rats in the sham-operated group and 8 rats in each of the other three groups were dissected to observe pathologic changes of the lung tissues, and the levels of serum TGF-beta1 and PDGF were determined by enzyme-linked immunosorbent assay. RESULTS: At the 45th day, the degree of pulmonary interstitial fibrosis was lesser in rats of the Feixian Formula-treated group as compared with those of the untreated group and prednisone-treated group. The levels of serum TGF-beta1 and PDGF were increased, and were significantly higher than those of the sham-operated group, especially on the 45th day (P<0.05). Changes of TGF-beta1 level in the prednisone-treated group and the Feixian Formula-treated group were similar to untreated group (P>0.05), and there was no significant difference between the prednisone-treated group and the Feixian Formula-treated group (P>0.05). PDGF in the Feixian Formula-treated group reached the highest level on the 14th day, significantly higher than those of the other three groups (P<0.01). Then it decreased, and was close to that of the sham-operated group on the 45th day (P=0.792). The levels of PDGF in untreated group and prednisone-treated group were increased depending on time, and were obviously higher than that of the sham-operated group on the 45th day (P<0.01). CONCLUSION: Feixian Formula can relieve bleomycin-induced pulmonary fibrosis in rats, and the mechanism of its action may be related to down-regulating serum PDGF.