miRNA-22 is involved in the aortic reactivity in physiological conditions and mediates obesity-induced perivascular adipose tissue dysfunction

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Balbino-Silva, Camila S. ; Couto, Gisele K. ; Lino, Caroline A. ; de Oliveira-Silva, Tabatha ; Lunardon, Guilherme ; Huang, Zhan-Peng ; Festuccia, William T. ; Barreto-Chaves, Maria Luiza ; Wang, Da-Zhi ; V. Rossoni, Luciana ; Diniz, Gabriela P.

• Document type: Journal article
• Source: Life Sciences; v. 316, p. 10-pg., 2023-01-26.

Abstract

Aims: Blood vessels are surrounded by perivascular adipose tissue (PVAT), which plays an important role in vascular tonus regulation due to its anticontractile effect; however, this effect is impaired in obesity. We previously demonstrated that miRNA-22 is involved in obesity-related metabolic disorders. However, the impact of miRNA-22 on vascular reactivity and PVAT function is unknown. Aim: To investigate the role of miRNA-22 on vascular reactivity and its impact on obesity-induced PVAT dysfunction. Main methods: Wild-type and miRNA-22 knockout (KO) mice were fed a control or a high-fat (HF) diet. To characterize the vascular response, concentration-responses curves to noradrenaline were performed in PVAT- or PVAT+ thoracic aortic rings in absence and presence of L-NAME. Expression of adipogenic and thermogenic markers and NOS isoforms were evaluated by western blotting or qPCR. Key findings: HF diet and miRNA-22 deletion reduced noradrenaline-induced contraction in PVAT- aortic rings. Additionally, miRNA-22 deletion increased noradrenaline-induced contraction in PVAT+ aortic rings without affecting its sensitivity; however, this effect was not observed in miRNA-22 KO mice fed a HF diet. Interestingly, miRNA-22 deletion reduced the contraction of aortic rings to noradrenaline via a NOS-dependent mechanism. Moreover, HF diet abolished the NOS-mediated anticontractile effect of PVAT, which was attenuated by miRNA22 deletion. Mechanistically, we found that PVAT from miRNA-22 KO mice fed a HF diet presented increased protein expression of nNOS. Significance: These results suggest that miRNA-22 is important for aorta reactivity under physiological circumstances and its deletion attenuates the loss of the NOS-mediated anticontractile effect of PVAT in obesity. (AU)

• FAPESP's process: 18/10338-2 - Role of microRNA-22 in differentiation of brown adipocytes and in browning of white adipose tissue
• Grantee: Gabriela Placoná Diniz
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/26657-0 - Impact of miRNA-22 in the vascular reactivity of obese mice
• Grantee: Camila Stephanie Balbino Silva
• Support Opportunities: Scholarships in Brazil - Master