期刊
PATHOLOGY RESEARCH AND PRACTICE
卷 203, 期 12, 页码 863-872出版社
ELSEVIER GMBH
DOI: 10.1016/j.prp.2007.08.006
关键词
hypertrophy; heart failure; focal adhesion kinase; neuronal nitric oxide synthase; matrix metalloproteinase
类别
Pulmonary hypertension induces right ventricular (RV) overload, which is transmitted to cardiomyocytes via integrins that activate intracellular messengers, including focal adhesion kinase (FAK) and neuronal nitric oxide synthase (NOSI). We investigated whether RV hypertrophy (RVH) and RV failure (RVF) were associated with activation of FAK, NOSI, and matrix metalloproteinases (MMPs). Rats were treated without (RVC or with a low dose of monocrotaline (30 mg/kg) to induce RVH, and with a high dose (80 mg/kg) to induce RVF. After,approximate to 30 days, RV function was determined using a combined pressure-conductance catheter. After sacrifice, FAK, NOSI, their phosphorylated forms (FAK-P and NOSI-P), MMP-2, and MMP-9 were quantified in RV myocardium by immunohistochemistry. In RVH and RVF, RV weight/ body weight increased by 36% and 109%, whereas RV ejection fraction decreased by 23% and 57% compared to RVC, respectively. FAK-P and FAK-P/FAK were highest in RVH (2.87 +/- 0.12 and 2.52 +/- 0.23 fold compared to RVC, respectively) and slightly elevated in RVF (1.76 +/- 0.17 and 1.15 +/- 0.13 fold compared to RVC, respectively). NOSI-P and NOSI-P/NOSI were increased in RVH (1.63 +/- 0.12 and 3.06 +/- 0.80 fold compared to RVC, respectively) and RVF (2.16 +/- 0.03 and 3.30 +/- 0.38 fold compared to RVC, respectively). MMP-2 was highest in RVH and intermediate in RVF (3.50 +/- 0.12 and 1.84 +/- 0.22 fold compared to RVC, respectively). MMP-9 was elevated in RVH and RVF (2.39 +/- 0.35 and 2.92 +/- 0.68 fold compared to RVC, respectively). Activation of FAK in RVH points to an integrin-dependent hypertrophic response of the myocardium. Activation of NOS I in failing RV suggests a role of excessive NO in the development of failure and activation of MMPs leading to ventricular remodeling. (c) 2007 Elsevier GmbH. All rights reserved.
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