Role of Neuropilin-1 in Pathogenesis of Cardiovascular Diseases

The Tumor Angiogenesis and Vascular Biology Lab is investigating the role of neuropilin-1 (NRP1) in the pathogenesis of cardiovascular diseases.

NRP1 is a multidomain receptor with functional roles in the cardiovascular system and involvement in neuronal development and the pathogenesis of cancer.

Scientists know that NRP1 binds several structurally diverse ligands, including vascular endothelial growth factors (VEGFs), and mediates different cellular functions.

However, the roles and the molecular mechanism of NRP1 in pathogenesis of cardiovascular diseases remain unclear.

Dr. Mukhopadhyay's lab uses transgenic mouse lines deficient of NRP1 in endothelial cells, cardiomyocytes and vascular smooth muscle cells, and several animal models, including a myocardial infarction model, to address the role of NRP1 in cardiovascular diseases.

The lab's research shows that mice lacking NRP1 in cardiomyocytes and vascular smooth muscle cells (SM22-α-Nrp-1 KO) exhibited decreased survival rates and developed cardiomyopathy and aggravated myocardial infarction-induced heart failure.

Deletion of NRP1 induced peroxisome proliferator-activated receptor γ coactivator 1α in cultured cardiomyocytes and vascular smooth muscle cells, which was accompanied by dysregulated cardiac mitochondrial accumulation and induction of cardiac hypertrophy-related markers and stress-related markers.

Importantly, SM22-α-Nrp-1 KO mice exhibited impaired physical activities and altered metabolite levels in serum, liver and adipose tissues, as demonstrated by global metabolic profiling analysis.

These results suggest that NRP1 signaling could be a promising target to modulate mitochondrial homeostasis in prevention and treatment of cardiac diseases and to provide insights about the role of cardiac metabolism in systemic metabolic disorders.