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Interleukin 10 (IL-10) is a probable anti-inflammatory factor that can attenuate hypertrophic remodelling caused by overloaded pressure and improve cardiac function. In this study, IL-10 was decreased in both the plasma of hypertensive patients and the aortic vessels of angiotensin II (Ang II)-induced hypertensive mice. IL-10 was unable to alter blood pressure in the case of Ang II-induced hypertension. The aortic thickness, collagen deposition, and the levels of fibrosis-associated markers, including collagen type I α 1 (Col1 α 1), connective tissue growth factor (CTGF), transforming growth factor- β (TGF- β ), and matrix metalloproteinase 2 (MMP2), were significantly reduced in the IL-10 treatment group compared with the vehicle group after Ang II treatment. Moreover, IL-10 treatment significantly inhibited the number of CD45 + positive cells and the mRNA expression levels of proinflammatory cytokines in the vascular tissue of Ang II-infused mice. Furthermore, dihydroethidium (DHE) and 4hydroxynonenal (4-HNE) staining showed that IL-10 decreased Ang II-induced vascular oxidative stress and lipid peroxidation. Furthermore, IL-10 suppressed Ang II-induced proliferation, fibrosis, and inflammation of mouse vascular adventitial fibroblasts (mVAFs). Mechanistically, IL-10 suppressed the phosphorylation of p38 mitogen-activated protein (MAP) kinase and nuclear factor- κ B (NF- κ B) in Ang II-induced vascular fibrosis. In summary, our data indicated that IL-10, as a potential therapeutic target treatment, could limit the progression of Ang II-induced aortic remodelling., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2022 Ming Qiu et al.)

Vascular events can trigger a pathological phenotypic switch in vascular smooth muscle cells (VSMCs), decreasing and disrupting the plasticity and diversity of vascular networks. The development of novel therapeutic approaches is necessary to prevent these changes. We aimed to investigate the effects and associated mechanisms of low-intensity pulsed ultrasound (LIPUS) irradiation on the angiotensin II (AngII)-induced phenotypic switch in VSMCs. In vivo, AngII was infused subcutaneously for 4 weeks to stimulate vascular remodeling in mice, and LIPUS irradiation was applied for 20 min every 2 days for 4 weeks. In vitro, cultured rat aortic VSMCs (RAVSMCs) were pretreated once with LIPUS irradiation for 20 min before 48-h AngII stimulation. Our results showed that LIPUS irradiation prevents AngII-induced vascular remodeling of the whole wall artery without discriminating between adventitia and media in vivo and RAVSMC phenotypic switching in vitro. LIPUS irradiation downregulated miR-17-5p expression and upregulated peroxisome proliferator-activated receptor gamma (PPAR-γ) expression. The PPAR-γ activator rosiglitazone could mimic the favorable effects of LIPUS irradiation on AngII-treated RAVSMCs. In contrast, GW9662 could impede the LIPUS-mediated downregulation of RAVSMC proliferation and inflammation under AngII stimulation conditions in vivo and in vitro. Also, the miR-17-5p agomir has the same effects as GW9662 in vitro. Besides, the inhibitory effects of GW9662 against the anti-remodeling effects of LIPUS irradiation in AngII-induced RAVSMCs could be blocked by pretreatment with the miR-17-5p antagomir. Overall, LIPUS irradiation prevents AngII-induced RAVSMCs phenotypic switching through hampering miR-17-5p and enhancing PPAR-γ, suggesting a new approach for the treatment of vascular disorders., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Alamandine attenuates hypertension and cardiac remodeling in spontaneously hypertensive rats (SHRs). We examined whether alamandine attenuates vascular remodeling in mice, and regulates angiotensin II (Ang II)-induced fibrosis in rat vascular smooth muscle cells (VSMCs). Alamandine attenuated hypertension in mice induced by Ang II. Ang II increased the fibrosis of thoracic aorta in mice, which was attenuated by alamandine treatment. Increased levels of collagen I, transforming growth factor-β (TGF-β), and connective tissue growth factor (CTGF) levels in thoracic aortas after Ang II treatment in mice were inhibited by alamandine. Ang II-stimulated collagen I, TGF-β, and CTGF level increases were inhibited by alamandine in rat VSMCs. This could be reversed by Mas-related G protein-coupled receptor, member D (MrgD) antagonist D-Pro 7 -Ang-(1-7) but not Mas receptor antagonist A779. MrgD expression was increased in the thoracic aortas of mice or VSMCs treatment with Ang II. Ang II increased p-p38 and cAMP levels in rat VSMCs, and alamandine blocked Ang II-induced these increases. Cyclic adenosine monophosphate (cAMP) reversed the inhibitory effects of alamandine on the Ang II-induced increases in collagen I, TGF-β, and CTGF levels. These results demonstrate alamandine attenuates vascular fibrosis by stimulating MrgD expression and decreases arterial fibrosis by blocking p-p38 expression. Alamandine/MrgD axis is a potential target for the treatment of vascular remodeling., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Alamandine (Ala), a ligand of Mas-related G protein-coupled receptor, member D (MrgD), alleviates angiotensin II (AngII)-induced cardiac hypertrophy. However, the specific physiological and pathological role of MrgD is not yet elucidated. Here, we found that MrgD expression increased under various pathological conditions. Then, MrgD knockdown prevented AngII-induced cardiac hypertrophy and fibrosis via inactivating Gαi-mediacted downstream signaling pathways, including the phosphorylation of p38 (p-P38), while MrgD overexpression induced pathological cardiac remodeling. Next, Ala, like silencing MrgD, exerted its cardioprotective effects by inhibiting Ang II-induced nuclear import of MrgD. MrgD interacted with p-P38 and promoted its entry into the nucleus under Ang II stimulation. Our results indicated that Ala was a blocking ligand of MrgD that inhibited downstream signaling pathway, which unveiled the promising cardioprotective effect of silencing MrgD expression on alleviating cardiac remodeling. 1vKXCZb4BaEYhFYZUPiv-d Video Abstract [ABSTRACT FROM AUTHOR]

Cardiac hypertrophy and fibrosis are the major causes of heart failure due to non‐ischaemia heart disease. To date, no specific therapy exists for cardiac fibrosis due to the largely unknown mechanisms of disease and lack of applicable therapeutic targets. In this study, we aimed to explore the role and associated mechanism of peptidase inhibitor 16 (PI16) in cardiac fibrosis induced by angiotensin II. In cardiac fibroblasts (CFs), overexpressed PI16 significantly inhibited CF proliferation and the levels of fibrosis‐associated proteins. Further analysis of epigenetic changes in CF revealed that overexpressed PI16 decreases the nuclear level of histone deacetylase 1 (HDAC1) after angiotensin II treatment, resulting in increased histone 3 acetylation in K18 and K27 lysine. However, overexpression of HDAC1 by an adenovirus vector in CFs reversed these changes. Echocardiography showed that PI16 transgenic (Tg) mice have smaller left ventricle mass than wild‐type mice. Histological analysis data showed that PI16 Tg mice demonstrated smaller cardiomyocyte size and less collagen deposition than wild‐type mice. The effects of PI16 on HDAC1 and histone 3 were also confirmed in PI16 Tg mice using immunostaining. Generally, PI16 is a HDAC1 regulator specifically in CFs, and PI16 overexpression prevents cardiac hypertrophy and fibrosis by inhibiting stress‐induced CF activation. [ABSTRACT FROM AUTHOR]