Your browser doesn't support javascript.
loading
Brown Adipocyte ADRB3 Mediates Cardioprotection via Suppressing Exosomal iNOS.
Lin, Jing-Rong; Ding, Li-Li-Qiang; Xu, Lian; Huang, Jun; Zhang, Ze-Bei; Chen, Xiao-Hui; Cheng, Yu-Wen; Ruan, Cheng-Chao; Gao, Ping-Jin.
Affiliation
  • Lin JR; Department of Cardiovascular Medicine, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, China (J.-R.L., L.-L.-Q.D., L.X., J.H., Z.-B.Z., X.-H.C., Y.-W.C., P.-J.G.)
  • Ding LL; Department of Cardiovascular Medicine, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, China (J.-R.L., L.-L.-Q.D., L.X., J.H., Z.-B.Z., X.-H.C., Y.-W.C., P.-J.G.)
  • Xu L; Department of Cardiovascular Medicine, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, China (J.-R.L., L.-L.-Q.D., L.X., J.H., Z.-B.Z., X.-H.C., Y.-W.C., P.-J.G.)
  • Huang J; Department of Cardiovascular Medicine, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, China (J.-R.L., L.-L.-Q.D., L.X., J.H., Z.-B.Z., X.-H.C., Y.-W.C., P.-J.G.)
  • Zhang ZB; Department of Cardiovascular Medicine, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, China (J.-R.L., L.-L.-Q.D., L.X., J.H., Z.-B.Z., X.-H.C., Y.-W.C., P.-J.G.)
  • Chen XH; Department of Cardiovascular Medicine, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, China (J.-R.L., L.-L.-Q.D., L.X., J.H., Z.-B.Z., X.-H.C., Y.-W.C., P.-J.G.)
  • Cheng YW; Department of Cardiovascular Medicine, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, China (J.-R.L., L.-L.-Q.D., L.X., J.H., Z.-B.Z., X.-H.C., Y.-W.C., P.-J.G.)
  • Ruan CC; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Shanghai Key Laboratory of Bioactive Small Molecules, Fudan University, China (C.-C.R.).
  • Gao PJ; Department of Cardiovascular Medicine, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, China (J.-R.L., L.-L.-Q.D., L.X., J.H., Z.-B.Z., X.-H.C., Y.-W.C., P.-J.G.)
Circ Res ; 131(2): 133-147, 2022 07 08.
Article in En | MEDLINE | ID: mdl-35652349
BACKGROUND: The ADRB3 (ß3-adrenergic receptors), which is predominantly expressed in brown adipose tissue (BAT), can activate BAT and improve metabolic health. Previous studies indicate that the endocrine function of BAT is associated with cardiac homeostasis and diseases. Here, we investigate the role of ADRB3 activation-mediated BAT function in cardiac remodeling. METHODS: BKO (brown adipocyte-specific ADRB3 knockout) and littermate control mice were subjected to Ang II (angiotensin II) for 28 days. Exosomes from ADRB3 antagonist SR59230A (SR-exo) or agonist mirabegron (MR-exo) treated brown adipocytes were intravenously injected to Ang II-infused mice. RESULTS: BKO markedly accelerated cardiac hypertrophy and fibrosis compared with control mice after Ang II infusion. In vitro, ADRB3 KO rather than control brown adipocytes aggravated expression of fibrotic genes in cardiac fibroblasts, and this difference was not detected after exosome inhibitor treatment. Consistently, BKO brown adipocyte-derived exosomes accelerated Ang II-induced cardiac fibroblast dysfunction compared with control exosomes. Furthermore, SR-exo significantly aggravated Ang II-induced cardiac remodeling, whereas MR-exo attenuated cardiac dysfunction. Mechanistically, ADRB3 KO or SR59230A treatment in brown adipocytes resulted an increase of iNOS (inducible nitric oxide synthase) in exosomes. Knockdown of iNOS in brown adipocytes reversed SR-exo-aggravated cardiac remodeling. CONCLUSIONS: Our data illustrated a new endocrine pattern of BAT in regulating cardiac remodeling, suggesting that activation of ADRB3 in brown adipocytes offers cardiac protection through suppressing exosomal iNOS.
Subject(s)
Key words
Fulltext
Add to My VHL
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Ventricular Remodeling / Adipocytes, Brown Limits: Animals Language: En Journal: Circ Res Year: 2022 Document type: Article Country of publication: United States
Fulltext
Add to My VHL
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Ventricular Remodeling / Adipocytes, Brown Limits: Animals Language: En Journal: Circ Res Year: 2022 Document type: Article Country of publication: United States