Cardiomyopathy and Worsened Ischemic Heart Failure in SM22-α Cre-Mediated Neuropilin-1 Null Mice. Issue 6 (June 2015)

• Record Type: Journal Article
• Authors: Wang, Ying; Cao, Ying; Yamada, Satsuki; Thirunavukkarasu, Mahesh; Nin, Veronica; Joshi, Mandip; Rishi, Muhammed T.; Bhattacharya, Santanu; Camacho-Pereira, Juliana; Sharma, Anil K.; Shameer, Khader; Kocher, Jean-Pierre A.; Sanchez, Juan A.; Wang, Enfeng; Hoeppner, Luke H.; Dutta, Shamit K.; Leof, Edward B.; Shah, Vijay; Claffey, Kevin P.; Chini, Eduardo N.; Simons, Michael; Terzic, Andre; Maulik, Nilanjana; Mukhopadhyay, Debabrata
• Is Part Of: Arteriosclerosis, thrombosis, and vascular biology. Volume 35:Issue 6(2015)
• Publication Date: 2015-06
• Subjects: Arteriosclerosis -- Periodicals; Thrombosis -- Periodicals; Blood-vessels -- Pathophysiology -- Periodicals; Electronic journals; 616.13
• DOI: 10.1161/ATVBAHA.115.305566
• Languages: English
• ISSNs: 1079-5642

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Objective—</title> <p>Neuropilin-1 (NRP-1) is a multidomain membrane receptor involved in angiogenesis and development of neuronal circuits, however, the role of NRP-1 in cardiovascular pathophysiology remains elusive.</p> </sec> <sec> <title>Approach and Results—</title> <p>In this study, we first observed that deletion of NRP-1 induced peroxisome proliferator–activated receptor γ coactivator 1α in cardiomyocytes and vascular smooth muscle cells, which was accompanied by dysregulated cardiac mitochondrial accumulation and induction of cardiac hypertrophy- and stress-related markers. To investigate the role of NRP-1 in vivo, we generated mice lacking <italic>Nrp-1</italic> in cardiomyocytes and vascular smooth muscle cells (SM22-α-<italic>Nrp-1</italic> KO), which exhibited decreased survival rates, developed cardiomyopathy, and aggravated ischemia-induced heart failure. Mechanistically, we found that NRP-1 specifically controls peroxisome proliferator–activated receptor γ coactivator 1 α and peroxisome proliferator–activated receptor γ in cardiomyocytes through crosstalk with Notch1 and Smad2 signaling pathways, respectively. Moreover, SM22-α-<italic>Nrp-1</italic> KO mice exhibited impaired physical activities and altered metabolite levels in serum, liver, and adipose tissues, as demonstrated by global metabolic profiling analysis.</p> </sec> <sec> <title>Conclusions—</title> <p>Our findings provide new insights into the cardioprotective role of NRP-1 and its influence on global metabolism.</p> </sec> </abstract>