Overlapping cardiac programs in heart development and regeneration.

Gaining cellular and molecular insights into heart development and regeneration will likely provide new therapeutic targets and opportunities for cardiac regenerative medicine, one of the most urgent clinical needs for heart failure. Here we present a review on zebrafish heart development and regeneration, with a particular focus on early cardiac progenitor development and their contribution to building embryonic heart, as well as cellular and molecular programs in adult zebrafish heart regeneration. We attempt to emphasize that the signaling pathways shaping cardiac progenitors in heart development may also be redeployed during the progress of adult heart regeneration. A brief perspective highlights several important and promising research areas in this exciting field.

[Recent progress in heart regeneration].

Heart failure (CHF) is the direct cause of death of a variety of cardiovascular diseases, culminating in irreversible myocardial necrosis and fibrosis. Traditional drug treatment, intervention, and surgical treatment have their own limitations. Increasing cardiac regeneration and repair of the injured heart is undoubtedly a promising approach to solve these clinical problems. In this paper, we summarized recent progress of heart development and regeneration, highlighting potential involvement of cell proliferation, dedifferentiation and cell reprogramming. We also proposed several fundamental and important research directions in this exciting area.

Association of intergenic polymorphism of organic anion transporter 1 and 3 genes with hypertension and blood pressure response to hydrochlorothiazide.

BACKGROUND: Organic anion transporter (OAT) 1 and OAT3, encoded by a tightly linked gene pair, play a key role in renal secretion of diuretics. However, no study has yet examined the influence of OAT1 and OAT3 polymorphisms on high blood pressure (BP) and the response to thiazide diuretics. We hypothesized that intergenic polymorphisms between OAT1 and OAT3 might be associated with adult hypertension and the antihypertensive effects of hydrochlorothiazide (HCTZ). METHODS: The association of an intergenic polymorphism (rs10792367) with hypertension risk was investigated in two independent case-control studies (n = 1,592 and 602), and then a combined analysis was performed for improving power (1,106 cases and 1,088 controls) with adjustment for geographic location. Two clinical trials (n = 542 and 274) were conducted in untreated hypertensive patients for the association of rs10792367 with antihypertensive responses to 4 and 8 weeks of HCTZ treatment. RESULTS: No significant association was found between rs10792367 and hypertension after adjustment for conventional risk factors in either the two populations, respectively, or the combined two population. After adjustment for pretreatment BP and other confounders, HCTZ-induced reduction in systolic BP was 4.8 mm Hg (P = 0.006, first trial) and 6.1 mm Hg (P = 0.003, in second trial) lower, respectively, in C allele carriers than in GG carriers in the two clinical trials. CONCLUSIONS: Intergenic polymorphism rs10792367 between OAT1 and OAT3 is not associated with hypertension, but appears to be involved in between-individual variations in antihypertensive responses to HCTZ.

Ghrelin receptor gene polymorphisms are associated with female metabolic syndrome in Chinese population.

BACKGROUND: The ghrelin plays an important role in the regulation of food intake and energy homeostasis. Therefore, the ghrelin receptor gene (GHSR) is an excellent candidate for studying metabolic syndrome. This study aimed to investigate whether polymorphisms in ghrelin receptor gene are associated with metabolic syndrome in Chinese population. METHODS: Subjects consisted of 698 patients aged 41 to 80 years, diagnosed as metabolic syndrome by International Diabetes Federation (IDF) 2005 criteria, and 762 age- and gender-matched controls. Three variants within the GHSR were selected and genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Odds ratios were estimated using a case-control study design by controlling confounding factors. RESULTS: The A/A genotype (rs2922126) in the promoter was associated with metabolic syndrome (OR 1.41, 95% CI 1.03-1.94), increased waist circumference (OR 1.75, 95% CI 1.26-2.42), and increased fast blood glucose (OR 1.49, 95% CI 1.07-2.06) in women. The A/A genotype (rs509030) in the intron was associated with lower plasma high density lipoprotein in women (OR 1.37, 95% CI 1.02-1.84). CONCLUSION: The polymorphisms within GHSR might be a genetic risk factor for metabolic syndrome in women.

Cardiovascular risk and prevalence of metabolic syndrome by differing criteria.

BACKGROUND: The prevalence of metabolic syndrome (MetS) in hypertensive population in Chinese countryside is unknown. Firstly, this study compared the prevalence of MetS according to National Cholesterol Education Program (NCEP) ATPIII, revised NCEP and International Diabetes Federation (IDF) definitions. Secondly, it investigated the association between MetS, coronary heart disease (CHD) and stroke in patients with hypertension. METHODS: In this cross sectional study, the cluster sampling method was used. Three MetS definitions were applied to 1418 normal subjects and 5348 hypertensive patients aged 40-75 years in rural areas in China. The agreement between different MetS definitions was estimated by kappa statistics. Logistic regression analyses determined the association between MetS defined by the three MetS definitions and CHD and stroke. RESULTS: In subjects without hypertension, the prevalence of Mets was 4.1% by NCEP definition, 8.3% revised NCEP definition and 7.8% IDF definition. In hypertensive individuals, the prevalence was 14.0%, 32.9%, and 27.4% in men; 35.6%, 53.1%, and 50.2% in women by the same definitions, respectively. In hypertensive individuals, the agreement was 94.4% in men and 97.0% in women between revised NCEP and IDF definitions. The IDF defined MetS was more strongly associated with CHD than the NCEP or revised NCEP defined MetS (adjusted odds ratio: 1.92 compared with 1.85 and 1.69 in men; 1.64 compared with 1.48 and 1.60 in women). CONCLUSIONS: In the patients with hypertension, the revised NCEP and IDF definitions identified more individuals than NCEP definition and their agreement is very high. The IDF defined MetS is more strongly associated with CHD than the NCEP or revised NCEP defined MetS, but weakly or not associated with stroke.

Interaction of genetic risk factors confers higher risk for thrombotic stroke in male Chinese: a multicenter case-control study.

Stroke is a polygenic or multifactorial disease, and each single susceptibility gene has modest effects. We hypothesize that combined effects of multiple genes might confer a higher stroke risk than a single susceptibility gene. To test our hypothesis we initially recruited 2000 stroke patients (44.3% thrombosis, 28.3% lacunar infarction and 27.4% intracerebral hemorrhage) and 2000 controls, and examined 6 polymorphisms in 5 candidate genes for stroke. Plasma lipoprotein(a) [Lp(a)] level was defined as a categorical variable and also included. Interactions between genetic risk factors were detected by the multifactor dimensionality reduction (MDR) method and further evaluated by multivariate logistic regression analyses. A significant combined effect on stroke due to the C677T polymorphism of methylenetetrahydrofolate reductase (MTHFR), the T2354A polymorphism of 5-lipoxygenase activating protein (ALOX5AP), and Lp(a) level, was detected using the MDR method. Furthermore, the combination of MTHFR 677TT, ALOX5AP 2354AA and Lp(a) elevation (Lp(a) concentration > or = 30 mg/dL) was found to be strongly associated with thrombotic stroke in males (OR, 10.419; 95%CI, 2.602 to 41.749; P= 0.001) using the multivariate logistic regression model. In conclusion, our results show that a combination of genetic risk factors can confer a higher risk for stroke than a single risk factor, indicating that people with multiple genetic risk factors have a higher risk of stroke and should be targets for prevention of this disease.

[A novel LMNA gene mutation E82K associated with familial dilated cardiomyopathy].

OBJECTIVE: To examine the function of the novel mutation E82K in LMNA gene identified in a Chinese family infected by dilated cardiomyopathy. METHODS: (1) One Chinese family infected by dilated cardiomyopathy was chosen for the study. Exons 1-12 of the LMNA gene were screened with both PCR method and the cycle sequencing of the PCR products. (2) cDNA of the E82K mutation or wild type of LMNA gene was transfected into HEK293 cells and the apoptosis of the cells was detected after treatment with 0.8 mmol/L H2O2. RESULTS: (1) A new mutation E82K in LMNA gene was identified in this dilated cardiomyopathy family. (2) Apoptosis was more in the HEK293 cells transfected with E82K mutation than those with empty vector or wild type LMNA gene. CONCLUSIONS: The missense mutation E82K in LMNA gene changed the polar of the amino acid. It showed a malignant phenotype of severe clinical symptoms, early onset, poor survival prognosis and might be associated with atrioventricular conduction block (II degrees-III degrees), suggesting that the E82K mutation in LMNA gene may be a candidate for nosogenesis of dilated cardiomyopathy.