Aims: Vascular peroxisome proliferator-activated receptor γ (PPARγ) activation improves vascular remodelling and endothelial function in hypertensive rodents. The goal of this study was to determine that vascular smooth muscle cell (VSMC) PPARγ exerts a vascular protective role beyond its metabolic effects.
Methods And Results: We generated a model of adult inducible VSMC-specific Pparγ inactivation to test the hypothesis that PPARγ counteracts angiotensin (Ang) II-induced vascular remodelling and endothelial dysfunction. Inducible VSMC Pparγ knockout mice were generated by crossing Pparγ floxed mice with mice expressing a tamoxifen-inducible Cre recombinase Smooth muscle (Sm) myosin heavy chain promoter control. Eight-to-ten-week-old SmPparγ(-/-) and control mice were infused with a nonpressor dose of Ang II for 7 days. Blood pressure was unaffected. Mesenteric arteries showed eutrophic remodelling in Ang II-infused control mice and hypertrophic remodelling in Ang II-infused SmPparγ(-/-) mice. Endothelium-dependent relaxation to acetylcholine was reduced in SmPparγ(-/-) mice and further impaired by Ang II infusion, and was unaffected by an inhibitor of NO synthase, suggesting a defect of NO-mediated relaxation. SmPparγ deletion increased the sensitivity to Ang II-induced contraction. SmPparγ(-/-) mice exhibited enhanced Ang II-induced vascular NADPH oxidase activity and adhesion molecule ICAM-1 and chemokine monocyte chemotactic protein-1 expression. The antioxidant Superoxide dismutase 3 expression was decreased by SmPparγ deletion. Ang II infusion increased the expression of CD3 T-cell co-receptor chain δ and decreased Adiponectin in perivascular adipose tissue of SmPparγ(-/-) mice.
Conclusion: Inducible Pparγ inactivation in VSMCs exacerbated Ang II-induced vascular remodelling and endothelial dysfunction via enhanced vascular oxidative stress and inflammation, revealing the protective role of VSMC PPARγ in angiotensin II-induced vascular injury.
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http://dx.doi.org/10.1093/cvr/cvs362 | DOI Listing |
Clin Transl Med
January 2025
Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Background: Sporadic aortic aneurysm and dissection (AAD) is a critical condition characterised by the progressive loss of vascular smooth muscle cells (VSMCs) and the breakdown of the extracellular matrix. However, the molecular mechanisms responsible for the phenotypic switch and loss of VSMCs in AAD are not fully understood.
Methods And Results: In this study, we employed a discovery-driven, unbiased approach.
Redox Biol
December 2024
Department of Biochemistry and Molecular Biology, School of Basic Medicine, Guizhou Medical University, Gui'an, 561113, Guizhou, PR China. Electronic address:
NADPH oxidase 1 (Nox1) is a major isoform of Nox in vascular smooth muscle cells (VSMCs). VSMC activation and extracellular matrix (ECM) remodelling induce abdominal aortic aneurysm (AAA). In this study, we aim to determine the role of Nox1 in the progression of AAA and explore the underling mechanism.
View Article and Find Full Text PDFJ Colloid Interface Sci
December 2024
Department of Vascular Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China. Electronic address:
Abdominal aortic aneurysm (AAA) is a chronic inflammation-driven disease characterized by aortic wall destruction and expansion, leading to high morbidity and mortality. However, previous drug treatments for its common risk factors have not achieved favorable results, and the early prevention and treatment is still the main clinical dilemma. Anti-inflammation therapy is a promising therapeutical method targeting its pathogenesis mechanism, but it has not been explored in depth.
View Article and Find Full Text PDFCell Mol Life Sci
December 2024
Institute for Fetology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
Background And Objectives: Maternal western-style diets that are high in glucose and fat have well-known cardiovascular effects on offspring, yet the combined influence of such diets during pregnancy is relatively less comprehended. This study investigates the impact of maternal high glucose and fat diet (HGF) on vascular constriction in offspring and the underlying mechanisms.
Methods And Results: Pregnant Sprague-Dawley rats were provided with either HGF or control diets.
Adv Healthc Mater
December 2024
Department of Vascular Surgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325027, P. R. China.
The abdominal aortic aneurysm (AAA) is a severe and complex condition characterized by the pathological dilation of the abdominal aorta. Current therapeutic strategies are limited, with surgical repair being the most effective intervention due to the lack of medications that can slow aneurysmal expansion or prevent adverse events. In this study, an innovative nanoplatform, Mn-UiO-66-NH@HA, designed to repair vascular smooth muscle cells (VSMCs), and the extracellular matrix (ECM) is developed, thereby enhancing arterial wall integrity.
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