Apr 8, 2014

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

Circulation Journal : Official Journal of the Japanese Circulation Society
Suvd NerguiHiroaki Shimokawa

Abstract

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. RV autopsy samples from 6 PH patients with RV failure against 3 age- and sex-matched controls were first examined. Next, RV remodeling in 2 mouse models of chronic hypoxia-induced PH with endothelial nitric oxide synthase-deficient (eNOS(-/-)) and collagenase-resistant knock-in (Col(R/R)) mice were examined. In humans, RV failure was associated with RV hypertrophy, interstitial and perivascular fibrosis, decreased RV capillary density and increased macrophage recruitment. Furthermore, immunostaining showed that perivascular matrix metalloproteinase-2 was increased in PH patients with RV failure. In animals, both hypoxic eNOS(-/-) and Col(R/R) mice developed a greater extent of RV hypertrophy, perivascular remodeling and macrophage infiltration compared with wild-type mice. Capillary rarefaction was developed in hypoxic eNOS(-/-) mice, while Col(R/R) mice were able to increase their capillary density in the RV in response to chronic hypoxia. Both mouse models showed increased autophagy even under normoxic condition. These...Continue Reading

Mentioned in this Paper

Collagen Metabolic Process
Biochemical Pathway
Perivascular Fibrosis
Left Ventricle Remodeling
Autopsy
Collagen Diseases
Cirrhosis
Interstitial
Hypertrophy
Matrix Metalloproteinase 2

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