Effect of renin-angiotensin-aldosterone system gene polymorphisms on blood pressure response to antihypertensive treatment

Background The renin-angiotensin-aldosterone system （RAAS） is important for the development of essential hypertension, and many antihypertensive drugs target it. This study was undertaken to determine whether polymorphisms in the renin-angiotensin-aldosterone system are related to the blood pressure （BP） response to diuretic treatment in a Chinese Han ethnic population. Methods Fifty-four patients with essential hypertension received hydrochlorothiazide （12.5 mg, once daily） as monotherapy for four weeks. Seven polymorphisms in RAAS genes were genotyped by gene chip technology. The relationship between these polymorphisms and the change in blood pressure was observed after the 4-week treatment. Results The patients with angiotensinogen （AGT） -6G allele showed a greater reduction in diastolic BP （P=- 0.025） and mean BP （P=-0.039） than those carrying AA genotype. Patients carrying aldosterone synthase （CYP11B2） CC genotype exhibited a greater BP reduction than those carrying CT and TT genotypes （systolic BP： P=- 0.030; diastolic BP： P=- 0.026; mean BP： P=-0.003）. In addition, patients with a combination of CYP11B2 CC genotype and angiotensin converting enzyme （ACE） D allele might have a more pronounced reduction of systolic BP than those with any other genotypic combinations of the two genes （P=0.007）. Conclusions AGT-6G allele, CYP11B2 -344CC genotype and its combination with ACE D allele are associated with BP response to hydrochlorothiazide treatment. Larger studies are warranted to validate this finding.

Heat shock protein 27 regulates oxidative stress-induced apoptosis in cardiomyocytes:mechanisms via reactive oxygen species generation and Akt activation

Background Increased reactive oxygen species （ROS） formation, which in turn promotes cardiomyocytes apoptosis, is associated with the pathogenesis and progression of various cardiac diseases such as ischemia and heart failure. Recent studies have shown that over expression of heat shock protein 27 （Hsp27） confers resistance to cardiac ischemia/reperfusion injury. However, not much is known about the regulation of myocyte survival by Hsp27. Methods The rat cardiac cell line H9c2, with a stable overexpression of Hsp27, was established, with empty vector transfected H9c2 cells as controls. Following the cells challenged by Hydrogen Peroxide （H2O2）, lactate dehydrogenase （LDH） release, apoptosis, intracellular ROS, cell morphology, mitochondrial transmembrane potential and the activation of serine/threonine kinase Akt were determined. Results Along with marked suppression of H2O2-induced injury by Hsp27 overexpression in H9c2 cells, ROS generation and the loss of mitochondrial membrane potential were also significantly depressed. Furthermore, augmented Akt activation was observed in Hsp27 overexpressed H9c2 cells following H2O2 exposure. Conclusions Hsp27 inhibits oxidative stress-induced H9c2 damage and inhibition of ROS generation and the augmentation of Akt activation may be involved in the protective signaling.