BmooMPα-I ameliorates aortic fibrosis and hypertrophy in 2K1C hypertensive rats by reducing matrix metalloproteinase-2 activity

Matrix metalloproteinase 2 (MMP-2) is the major MMP involved in hypertension and plays a central role in vascular remodeling in response to hemodynamic changes by promoting upregulation of transforming growth factor beta 1 (TGF-β1), vascular hypertrophy, fibrosis, and oxidative stress. BmooMPα-I, a metalloproteinase isolated from Bothrops moojeni venom, exhibits kininogenase activity, is capable of hydrolyzing angiotensin I, and exerts antihypertensive and cardioprotective effects. This study evaluated the effect of BmooMPα-I on MMP-2 activity and expression, TGF-β1 expression, redox balance, and vascular remodeling in the aorta of two-kidney, one-clip (2K1C) hypertensive rats. Male Wistar rats (180-200g) underwent 2K1C surgery, and Sham animals underwent the same procedure without the arterial clip. After two weeks, animals were divided into four groups: Sham vehicle (saline), Sham BmooMPα-I 1μg/kg, 2K1C vehicle, and 2K1C BmooMPα-I 1μg/kg. Animals were treated daily for two weeks. A sustained increase in systolic blood pressure (SBP) was observed in 2K1C animals, accompanied by increased activity and expression of MMP-2 and TGF-β1, oxidative stress, vascular remodeling, and fibrosis in the aorta compared to Sham animals (p < 0.05). After two weeks of BmooMPα-I treatment, 2K1C animals showed a significant reduction in SBP, along with decreased MMP-2 activity and expression, as well TGF-β1 levels. Additionally, BmooMPα-I reversed oxidative stress, hypertrophy, and collagen deposition in the aorta compared to the 2K1C vehicle group (p < 0.05), reaching values similar to Sham (p < 0.05). We conclude that BmooMPα-I exerts an antihypertensive effect and reduces MMP-2 activity and expression, negatively modulates TGF-β1 expression, and reverses oxidative stress, vascular remodeling, and fibrosis. • BmooMPα-I, a metalloproteinase isolated from Bothrops moojeni venom, acts as a modulator of MMP-2 and exerts antihypertensive effects in the 2K1C model. • BmooMPα-I reduces oxidative stress in the thoracic aorta. • BmooMPα-I attenuates hypertension-induced vascular hypertrophy, TGF-β1 expression, and fibrosis.