To date, endothelial dysfunction is defined by a constellation of phenotypes including up-regulation of pro-inflammatory pathways, enhanced thrombogenicity, increased reactive oxygen species and reduced NO synthesis/bioavailability1, 2. Our lab has focused on the latter pathway by understanding how endothelial nitric oxide synthase (eNOS), the exclusive source of endothelial derived NO as a relaxing factor for smooth muscle, is regulated and these studies have led to the discovery of additional pathways that regulate several aspects of endothelial cell biology and function3. Thus, the central goal for this grant is to integrate advances derived from our previous work on eNOS to explore a broader range of pathways that can improve endothelial and vascular health.
This research is relevant to public health since we have endothelial dysfunction occurs in the blood vessels of patients with cardiovascular disease. Understanding how nitric oxide is released from blood vessels can lead to new therapeutic approaches for heart disease.
|Luciano, Amelia K; Zhou, Wenping; Santana, Jeans M et al. (2018) CLOCK phosphorylation by AKT regulates its nuclear accumulation and circadian gene expression in peripheral tissues. J Biol Chem 293:9126-9136|
|Zhang, Xinbo; Sessa, William C; Fernández-Hernando, Carlos (2018) Endothelial Transcytosis of Lipoproteins in Atherosclerosis. Front Cardiovasc Med 5:130|
|Lee, Monica Y; Gamez-Mendez, Ana; Zhang, Jiasheng et al. (2018) Endothelial Cell Autonomous Role of Akt1: Regulation of Vascular Tone and Ischemia-Induced Arteriogenesis. Arterioscler Thromb Vasc Biol 38:870-879|