Implication of PDGF signaling in cigarette smoke-induced pulmonary arterial hypertension in rat

Abstract

Pulmonary artery hypertension (PAH) is a severe disease characterized with progressive increase of pulmonary vascular resistance that finally causes right ventricular failure and premature death. Cigarette smoke (CS) is a major factor of Chronic Obstructive Pulmonary Disease (COPD) that can lead to PAH. However, the mechanism of CS-induced PAH is poorly understood. Mounting evidence supports that pulmonary vascular remodeling play an important role in the development of PAH. PDGF signaling has been demonstrated to be a major mediator of vascular remodeling implicated in PAH. However, the association of PDGF signaling with CS-induced PAH has not been documented. In this study, we investigated CS-induced PAH in rats and the expression of platelet derived growth factor (PDGF) and PDGF receptor (PDGFR) in pulmonary artery. Forty male rats were randomly divided into control group and three experimental groups that were exposed to CS for 1, 2, and 3 months, respectively. CS significantly increased right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVHI). Histology staining demonstrated that CS significantly increased the thickness of pulmonary artery wall and collagen deposition. The expression of PDGF isoform B (PDGF-B) and PDGF receptor beta (PDGFRβ) were significantly increased at both protein and mRNA levels in pulmonary artery of rats with CS exposure. Furthermore, Cigarette smoke extract (CSE) significantly increased rat pulmonary artery smooth muscle cell (PASMC) proliferation, which was inhibited by PDGFR inhibitor Imatinib. Thus, our data suggest PDGF signaling is implicated in CS-induced PAH.

Platelet-Derived Growth Factor Signaling in the Lung. From Lung Development and Disease to Clinical Studies

“…Zhao and colleagues confirmed PDGF-BB-induced proliferation and survival of pulmonary artery smooth muscle cells and showed that this effect was mediated by JNK pathway activation (166). Moreover, Xing and colleagues demonstrated that PDGF signaling plays a role in cigarette smoke-induced PAH and observed higher expression levels of PDGF-B and PDGFRb in pulmonary arteries of rats exposed to cigarette smoke compared with control rats (167).…”

Activation of renin–angiotensin–aldosterone system (RAAS) in the lung of smoking-induced pulmonary arterial hypertension (PAH) rats

“…1 Animal experiments demonstrated that chronic cigarette exposure may cause lung parenchyma and airway inflammation, and induce the reconstruction of small pulmonary vessels and small airway, resulting in pulmonary arterial hypertension. 2,3 Previous studies have reported that activation of the renin-angiotensin-aldosterone system (RAAS) system was involved in the pathogenesis of pulmonary vascular remodeling and PAH. 4,5 The expression of angiotensin-converting enzyme (ACE) increased in the pulmonary arterial of patients with PAH.…”

Perioperative Considerations of Patients with Pulmonary Hypertension

“…Furthermore, Cigarette smoke extract significantly increased rat pulmonary artery smooth muscle cell (PASMC) proliferation, which was inhibited by PDGFR inhibitor Imatinib. Thus, their results indicated PDGF signaling is also implicated in CS-induced PH [26].…”

“…There were no perinatal death, nine live births and three first-trimester miscarriages. Mean birthweight was 2197 grams, mean gestational age was 34 weeks (range [26][27][28][29][30][31][32][33][34][35][36][37][38][39], and mean birthweight percentile was 36 (range 5-60). Five babies required admission to the neonatal intensive care unit, but were all eventually discharged home.…”