PDF《The association between BMP4 gene》

RESEARCH Open Access The association between BMP4 gene polymorphism and its serum level with the incidence of LVH in hypertensive patients GL Gu1* , QY Yang2 , RL Zeng3 and XL Xu4 Abstract Background: Bone morphogenic proteins

4 (BMP4) is associated with cardiac remodeling under different conditions.

However, the role of BMP4 and its gene polymorphism in the incidence of left ventricular hypertrophy (LVH) in hypertensive patients remains unknown. Methods: A total of

1265 patients diagnosed with essential hypertension (EH) were recruited. Patients were assigned to LVH+ (n = 420) and LVH- (n = 845) groups. serum BMP4 level was measured and two single nucleotide polymorphism (SNPs) polymorphisms, 6007C >

T and -5826G >

A of BMP4 gene were genotyped. We also inhibited the BMP4 by small interfering RNA (siRNA). The effect of BMP4 on the hypertrophic response in Human Cardiomyocytes AC16 cells was studied. Results: We found that the 6007C >

T polymorphism of the BMP4 gene and the serum BMP4 level were significantly associated with the risk to develop LVH. With TT as reference, multivariate logistic regression analysis showed the 6007CC genotype carriers had a higher susceptibility to LVH incidence (adjusted OR = 2.65, 95% CI: 1.63-4.31, adjusted P <

0.001). Our in vitro study shows that the BMP4 inhibition in cardiomyocyte by si-RNA technique significantly decreased the Ang II induced cardiomyocyte size and protein content per cell, indicating the importance of BMP4 in the cardiomyocyte hypertrophy. Conclusion: Collectively, our data suggest that both the 6007C >

T of the BMP4 gene and the serum BMP4 level may be used as potential marker for LVH incidence among the EH patients. Keywords: Bone morphogenic proteins 4, Essential hypertension, Left ventricular hypertrophy, Small interfering RNA Background Left ventricular hypertrophy (LVH) is one of the major complication of high blood pressure, which is regarded as an independent risk factor for cardiovascular morbidity and mortality [1-4]. The established risk factors responsible for LVH includes blood pressure level, duration of hyper- tension, age, obesity, diet, and pharmacologic treatment [5,6]. In addition, a large body of evidence shows that the individual genetic background predisposes the LVH inci- dence [7-9]. Identifying the key factor mediating patho- logical cardiac hypertrophy is critically important for developing the strategy to protect against heart failure. BMP4 is a member of bone morphogenic proteins (BMP) superfamily, regulating osteoblast differentiation and bone formation [10-13]. In addition, BMP4 is a mechanosensitive and proinflammatory gene, and it in- duces endothelial cell apoptosis, and endothelium dysfunc- tion [14,15]. BMP4 induces cardiomyocyte differentiation and promotes cardiomyocyte apoptosis after ischemia- reperfusion injuryCinduced myocardial infarction [16,17]. The association between BMP4 and cardiac remodeling is recently reported. BMP4 is expressed in human and mouse hearts and recombinant BMP4 protects adult mouse car- diomyocytes against hypoxia-reoxygenation injury [18]. BMP4 induces cardiomyocyte hypertrophy and apoptosis through increasing nadph oxidase

4 expression and react- ive oxygen species-dependent pathways [19]. * Correspondence: [email protected]

1 Department of cardiovascular diseases, Jiangyin Hospital of traditional Chinese medicine affiliated Nanjing University of Chinese Medicine, Jiangyin 214400, Jiangsu, China Full list of author information is available at the end of the article ?