This is a revised new Program Project application from an interactive group of experienced investigators consisting of 3 projects and 3 cores. The overall theme of this PPG is to understand how arterioles are regulated by interactions between cell integrins and extracellular matrix (ECM) proteins and how these interactions are disturbed by vascular disease. Over the last 12 years, program investigators published most of the early work establishing a key role for integrins in microvascular control. Recent insights by our investigative team have identified key integrins and ECM proteins setting the stage for major breakthroughs in this field that will significantly advance our understanding of this paradigm for microvascular control. A central premise of this PPG is that microvascular control in health and disease is influenced by properties of the ECM and ECM interactions with integrins on cells of the microvascular wall. Project 1 will examine the ability of vasoactive mediators to influence integrin-ECM adhesion and determine how adhesion is coordinated with microvascular smooth muscle cell (mVSMC) contraction and control of arteriole diameter. Project 2 will examine the ability of ECM proteins to signal through integrins and modulate Mvsmc membrane conductance of Ca2+ and K+ to control vasomotor tone. Project 3 examines a unique hypothesis that during inflammation emigrating leukocytes cause ECM degradation that generates integrin-binding signals that impair control of arterioles. Core A will provide administrative support for the PPG. For all projects, Cores B will provide imaging technology/support and Core C will provide for molecular and cell level technologies. Together, the projects will shape an integrated view of microvascular regulation using model systems that include freshly isolated mVSMC, isolated arterioles and microvascular network preparations. A multidisciplinary array of technical approaches ranging from atomic force microscopy, fluorescence microscopy, electrophysiology and molecular techniques will allow a comprehensive and systematic exploration of concepts.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
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Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Program Officer
Mcdonald, Cheryl
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University of Missouri-Columbia
Schools of Medicine
United States
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Korthuis, Ronald J (2018) Mechanisms of I/R-Induced Endothelium-Dependent Vasodilator Dysfunction. Adv Pharmacol 81:331-364
Sun, Zhe; Li, Min; Li, Zhaohui et al. (2017) N-Cadherin, a novel and rapidly remodelling site involved in vasoregulation of small cerebral arteries. J Physiol 595:1987-2000
Hong, Kwangseok; Li, Min; Nourian, Zahra et al. (2017) Angiotensin II Type 1 Receptor Mechanoactivation Involves RGS5 (Regulator of G Protein Signaling 5) in Skeletal Muscle Arteries: Impaired Trafficking of RGS5 in Hypertension. Hypertension 70:1264-1272
Dai, Hongyan; Wang, Meifang; Patel, Parag N et al. (2017) Preconditioning with the BKCa channel activator NS-1619 prevents ischemia-reperfusion-induced inflammation and mucosal barrier dysfunction: roles for ROS and heme oxygenase-1. Am J Physiol Heart Circ Physiol 313:H988-H999
Foote, Christopher A; Castorena-Gonzalez, Jorge A; Staiculescu, Marius C et al. (2016) Brief serotonin exposure initiates arteriolar inward remodeling processes in vivo that involve transglutaminase activation and actin cytoskeleton reorganization. Am J Physiol Heart Circ Physiol 310:H188-98
Higashi, Yusuke; Sukhanov, Sergiy; Shai, Shaw-Yung et al. (2016) Insulin-Like Growth Factor-1 Receptor Deficiency in Macrophages Accelerates Atherosclerosis and Induces an Unstable Plaque Phenotype in Apolipoprotein E-Deficient Mice. Circulation 133:2263-78
Kalogeris, Theodore; Baines, Christopher P; Krenz, Maike et al. (2016) Ischemia/Reperfusion. Compr Physiol 7:113-170
Hong, Kwangseok; Zhao, Guiling; Hong, Zhongkui et al. (2016) Mechanical activation of angiotensin II type 1 receptors causes actin remodelling and myogenic responsiveness in skeletal muscle arterioles. J Physiol 594:7027-7047
Wang, Derek Z; Jones, Allan W; Wang, Walter Z et al. (2016) Soluble guanylate cyclase activation during ischemic injury in mice protects against postischemic inflammation at the mitochondrial level. Am J Physiol Gastrointest Liver Physiol 310:G747-56
Manrique, Camila; Habibi, Javad; Aroor, Annayya R et al. (2016) Dipeptidyl peptidase-4 inhibition with linagliptin prevents western diet-induced vascular abnormalities in female mice. Cardiovasc Diabetol 15:94

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