The key role of apoptosis in the pathogenesis and treatment of pulmonary hypertension

Abstract

In recent years, the process of the programmed cell death has gained much interest because it has important pathophysiological consequences contributing to the deletion of unwanted cells in the vessel wall, loss of pulmonary smooth muscle cells and therefore in reversing the pulmonary pressure. For the reason that most patients with pulmonary hypertension present with limited reversibility with vasodilators, antiremodeling approach for treatment appears to be feasible. Induction or enhancement of vascular smooth muscle cells apoptosis may be targeted to develop novel therapeutic approaches for pulmonary vascular remodeling in patients with pulmonary hypertension. This review summarizes the current mechanisms, investigate the roles and provide novel insights into the potential therapeutic value of apoptosis in the pulmonary artery remodeling of pulmonary hypertension.

Caspase-1, -2, and -3 gene expression is enhanced in the heart and lung of chickens with pulmonary hypertension (ascites)

“…It has been reported that apoptosis is involved in pathophysiology and pathogenesis of mammal pulmonary hypertension and free radicals are an important factor in activation of caspases and induction of apoptosis (10). Progressive hypoxia developing in chickens with pulmonary hypertension can cause increased free radicals that influence the metabolic systems, including cardiac systems, in pulmonary hypertensive birds (1,24,25).…”

“…The pathogenesis of pulmonary hypertension is a complicated, multifactorial process in which the combined effects of pulmonary artery vasoconstriction, vascular remodeling, and thrombosis are involved in a continuous high pulmonary vascular resistance (7)(8)(9). Vascular remodeling is associated with low-grade inflammation, vascular fibrosis, and apoptosis (10).…”

“…At the cellular and molecular levels, apoptosis is identified by morphological and biochemical changes such as cell shrinkage, formation of apoptotic bodies, caspase activation, chromatin condensation, and DNA fragmentation (10,12). Many molecular processes of apoptosis are mainly mediated by particular cysteine proteases named caspase.…”

“…Multicellular organisms regularly eliminate and renew cells to maintain their homeostasis. Abnormal function of this process has been implicated in atherosclerosis, cancer, heart failure, and pulmonary hypertension (10,11).…”

The effects of atorvastatin on pulmonary arterial hypertension and expression of p38, p27, and Jab1 in rats

“…However, accumulated data suggest that statins improve cardiovascular outcomes not only by lowering cholesterol but through other beneficial effects on the vascular wall (7,8). Statins improve endothelial function (9), promote angiogenesis (10) and apoptosis (11)(12)(13)(14), and reduce inflammation and pulmonary vascular remodeling (8). Statins may also act as antioxidants and antiproliferative (15,16) and antithrombolytic agents by inhibiting the formation of microthrombi and inhibiting endothelin-1 (ET-1), angiotensin (ANGII), and thromboxane A2 (TXA2) (17).…”