Angiotensin-(1–7) counteracts the effects of Ang II on vascular smooth muscle cells, vascular remodeling and hemorrhagic stroke: Role of the NFкB inflammatory pathway

Abstract

Angiotensin (Ang)-(1-7) is a potential vasoprotective peptide. In the present study, we investigated its counteractive effects to Ang II on vascular smooth muscle cells (VSMCs) and intracerebral hemorrhagic stroke (ICH) through inflammatory mechanism. In in vitro experiments, human brain VSMCs (HBVSMCs) were treated with vehicle, Ang II, Ang II + Ang-(1-7), Ang II + A-779 or Ang II + Ang-(1-7) + A-779 (Mas receptor antagonist). HBVSMC proliferation, migration and apoptosis were determined by methyl thiazolyltetrazolium, wounding healing assay and flow cytometry, respectively. In in vivo experiments,C57BL/6 mice were divided into vehicle, Ang II, Ang II + Ang-(1-7), Ang II + A-779 or Ang II + Ang-(1-7) + A-779 groups before they were subjected to collagenase-induced ICH or sham surgery. Hemorrhage volume and middle cerebral artery (MCA) remodeling were determined by histological analyses. Levels of NFκB, Inhibitor of κBα (IκBα), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein 1 (MCP-1) and interleukin (IL-8) were measured by western blot or ELISA. We found that 1) Ang II increased HBVSMC migration, proliferation and apoptosis, and increased the blood pressure (BP), neurological deficit score, MCA remodeling and hemorrhage volume in ICH mice. 2) Ang-(1-7) counteracted these effects of Ang II, which was independent of BP, with the down-regulation of NFκB, up-regulation of IκBα, and decreased levels of TNF-α, MCP-1 and IL-8. 3) The beneficial effects of Ang-(1-7) could be abolished by A-779. In conclusion, Ang-(1-7) counteracts the effects of Ang II on ICH via modulating NFκB inflammation pathway in HBVSMCs and cerebral microvessels.

Association Between Serum Phosphate Levels and Stroke Risk in Patients Undergoing Hemodialysis

“…Vascular inflammation has been shown to induce brain hemorrhage in both humans and animal models. 26,27 Phosphate loading directly induced inflammation in vascular smooth muscle cells and increased the expression of matrix metalloproteinases II and IX and cathepsin S, 28,29 which degrade extracellular matrix and disrupt the integrity of vascular layers. Furthermore, phosphate loading also induced the apoptosis of vascular smooth muscle cells and endothelial cells via oxidative stress and inflammation.…”

“…On the other hand, other investigators showed that higher serum PTH tended to decrease the risk of brain infarction. 26 Given that malnourished subjects often show lower serum PTH levels, low PTH might, thus, be a manifestation of malnutrition, which is in turn associated with brain infarction. 35 The protein catabolic rate is often increased during inflammation, and a higher normalized protein catabolic rate might reflect systemic inflammation, which is in turn associated with an increased risk of brain infarction.…”

Coronary microvascular disease as an early culprit in the pathophysiology of diabetes and metabolic syndrome

“…Indeed, studies from our laboratory demonstrate that AngII/AT 1 R activation may contribute to the vascular remodeling observed in T2D (11). Additionally, this AT 1 R-mediated activation of the VSMC by pro-inflammatory signaling may contribute to remodeling present in metabolic diseases (75, 76). …”

Regulation of Hypertension for Secondary Prevention of Stroke: The Possible ‘Bridging Function' of Acupuncture

“…Collagen induced atherothrombosis [80]. Ang II was involved in apoptosis, inflammation [81], the neurological deficit score, hemorrhage volume [82], hypertrophy, and inward remodeling of cerebral arterioles [83]; after decreasing the Ang II levels, cerebral blood supply was improved [84], and ET-1 may promote the development of the stroke process [85]. ETAR and NO may be involved in the pathogenesis of cerebral vasospasm [37].…”