Abstract
Background: Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary vascular resistance, leading to right ventricular failure and death. Recent studies have suggested that chronic inflammatory processes are involved in the pathogenesis of PAH. Several studies have demonstrated that betaine possesses outstanding anti-inflammatory effects. However, whether betaine exerts protective effects on PAH by inhibiting inflammatory responses in the lungs needs to be explored. To test our hypothesis, we aimed to investigate the effects of betaine on monocrotaline-induced PAH in rats and attempted to further clarify the possible mechanisms. Methods: PAH was induced by monocrotaline (50 mg/kg) and oral administration of betaine (100, 200, and 400 mg/kg/day). The mean pulmonary arterial pressure, right ventricular systolic pressure, and right ventricle hypertrophy index were used to evaluate the development of PAH. Hematoxylin and eosin staining and Masson staining were performed to measure the extents of vascular remodeling and proliferation in fibrous tissue. Monocyte chemoattractant protein-1 (MCP-1) and endothelin-1 (ET-1) were also detected by immunohistochemical staining. Nuclear factor-κB (NF-κB), tumor necrosis factor alpha (TNF-α), and interleukin-1β (IL-1β) were assessed by Western blot. Results: This study showed that betaine improved the abnormalities in right ventricular systolic pressure, mean pulmonary arterial pressure, right ventricle hypertrophy index, and pulmonary arterial remodeling induced by monocrotaline compared with the PAH group. The levels of MCP-1 and ET-1 also decreased. Western blot indicated that the protein expression levels of NF-κB, TNF-α, and IL-1β significantly decreased (p < 0.01). Conclusion: Our study demonstrated that betaine attenuated PAH through its anti-inflammatory effects. Hence, the present data may offer novel targets and promising pharmacological perspectives for treating monocrotaline-induced PAH.
Highlights
Pulmonary arterial hypertension (PAH) is a refractory disease defined by a mean pulmonary artery pressure at or above 25 mmHg; it is characterized by elevated pulmonary vascular
We evaluated the effects of betaine on MCT-induced lung and heart injury by detecting the mean pulmonary artery pressure (mPAP), right ventricular systolic pressure, and right ventricular hypertrophy (RVH) index (RVHI = right ventricle (RV)/(LV + S))
In the MCT group, obvious RV systolic pressure (RVSP) elevation developed as a consequence of increased pulmonary arterial pressures
Summary
Pulmonary arterial hypertension (PAH) is a refractory disease defined by a mean pulmonary artery pressure (mPAP) at or above 25 mmHg; it is characterized by elevated pulmonary vascularMolecules 2018, 23, 1274; doi:10.3390/molecules23061274 www.mdpi.com/journal/moleculesMolecules 2018, 23, 1274 resistance and arterial pressures and driven by a progressive pulmonary vasculopathy that leads to right ventricular hypertrophy (RVH), right ventricular failure, and death [1,2].The pathogenic mechanisms underlying PAH include vascular remodeling, inflammation, vasoconstriction, and thrombosis; PAH is generally assumed to involve an interaction of multiple factors [3]. Molecules 2018, 23, 1274 resistance and arterial pressures and driven by a progressive pulmonary vasculopathy that leads to right ventricular hypertrophy (RVH), right ventricular failure, and death [1,2]. The excessive proliferation of pulmonary arterial smooth muscle cells and perivascular inflammation lead to PAH progression, but they are not targeted by current therapies [7]. Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary vascular resistance, leading to right ventricular failure and death. Recent studies have suggested that chronic inflammatory processes are involved in the pathogenesis of PAH. Several studies have demonstrated that betaine possesses outstanding anti-inflammatory effects. Whether betaine exerts protective effects on PAH by inhibiting inflammatory responses in the lungs needs to be explored. We aimed to investigate the effects of betaine on monocrotaline-induced PAH in rats and attempted to further clarify the possible mechanisms
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