Role of endothelial nitric oxide synthase and collagen metabolism in right ventricular remodeling due to pulmonary hypertension.

Background: Pulmonary hypertension (PH) causes elevated right ventricular (RV) systolic pressure, RV remodeling and finally RV failure to death. However, the mechanisms of RV remodeling in PH remain to be fully elucidated.

Methods And Results: RV autopsy samples from 6 PH patients with RV failure against 3 age- and sex-matched controls were first examined.

Combination therapy with atorvastatin and amlodipine suppresses angiotensin II-induced aortic aneurysm formation.

Background: Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease. It is controversial whether statin and calcium channel blockers (CCBs) has an inhibitory effect on the expansion of AAA. Some studies reported that CCBs have an inhibitory effect on Rho-kinase activity.

Rho-kinase activation in patients with heart failure.

Background: Heart failure (HF) is a complex clinical syndrome, resulting from structural and/or functional cardiac disease. The aim of this study was to determine whether the activity of Rho-kinase, which has been identified as an important therapeutic target of cardiovascular disease, is enhanced in HF patients.

Methods And Results: Total and phosphorylated forms of myosin binding subunit (t-MBS and p-MBS), a substrate of Rho-kinase, were measured on western blotting in circulating leukocytes, and the p-MBS/t-MBS ratio was defined as an index of systemic Rho-kinase activity.

Ezetimibe improves endothelial function and inhibits Rho-kinase activity associated with inhibition of cholesterol absorption in humans.

Background: Ezetimibe is an inhibitor of cholesterol absorption in the intestine. We examined whether ezetimibe improves endothelial function, and if so, what mechanisms are involved.

Methods And Results: Nineteen healthy subjects (male/female 14/5; mean age, 31±3 [SD] years-old) were randomized to receive ezetimibe (10mg/day) or pravastatin (10mg/day) for 4 weeks in a cross-over manner with a 4-week washout interval.

Intensive immunosuppressive therapy improves pulmonary hemodynamics and long-term prognosis in patients with pulmonary arterial hypertension associated with connective tissue disease.

Background: Pulmonary arterial hypertension (PAH) remains a serious disease characterized by elevated pulmonary artery pressure (PAP) and increased pulmonary vascular resistance (PVR). Among its subtypes, PAH associated with connective tissue disease (CPAH) has the worse prognosis, because of resistance to conventional vasodilator therapy. We hypothesized that intensive immunosuppressive therapy (IIT) could improve the pulmonary hemodynamics in CPAH.

Evidence for Rho-kinase activation in patients with pulmonary arterial hypertension.

Background: Direct evidence for Rho-kinase activation in patients with pulmonary hypertension (PH) is still lacking.

Methods And Results: Rho-kinase activity in circulating neutrophils was examined by determining the ratio of phosphorylated/total forms of myosin-binding subunit, a substrate of Rho-kinase, in 40 consecutive PH patients and 40 healthy controls. Next, Rho-kinase expression and activity was examined in isolated human lung tissues (5 patients with idiopathic pulmonary arterial hypertension [IPAH], 5 controls) and vascular reactivity of isolated small human pulmonary arteries in vitro (4 IPAH, 4 controls).