The overall objective of the Grant in the past was to characterize the inflammatory response and inflammatory injury after reperfusion of the infarcted myocardium. In recent years, we have shifted our emphasis to include the role of inflammation in cardiac repair and cytoprotection. We hypothesize that the cellular and molecular components of cardiac inflammation evolved as a protective mechanism for the organism with a potential role in tissue repair and cytoprotection. We hypothesize that the cellular and molecular components of cardiac inflammation evolved as a protective mechanism for the organism with a potential role in tissue repair and cytoprotection. Project 1 examines three reperfusion dependent events, which may modulate tissue: 1) Phenotypic transition of neutrophils as a major source of fibrogenic and angiogenic factors, 2) Mast cell recruitment in tissue repair and scar formation, and 3) Reperfusion dependence of early chemokine induction in cardiac venular endothelial and its downstream significance. Project 2 utilizes genetic deletions of specific cell adhesion molecular to define: 1) cardiac specific molecular mechanisms regulating leukocyte trafficking, 2) differences between cardiac microvascular endothelium and venous endothelium, 3) novel pathways for primary adhesion of leukocytes which are independent of known selectins, and 4) the role of cell adhesion molecules in tissue repair of the heart. Project 3 examines both positive and negative controllers of leukocyte adhesion and trafficking focusing on 1) shear dependent activation of leukocyte functions effected by selectin binding, the role of LFA-1 under shear and novel factors in adhesion and signaling. Project 4 is a new project which arises from work in the current grant period that demonstrated reperfusion-dependent induction of myocyte cytokines (TNF-alpha), IL-6, and LIF). Studies in the current grant period, suggest that inflammatory cytokines could potentially by cytoprotective. The project will study the mechanism of these cytoprotective effects specifically focusing on their anti-apoptotic effects of the molecular basis for them. The projects share methods and experimental paradigms. In addition to an Administrative Core, the application continues the Animal Core and Cell Biology Core that have produce many of our unique models.
| Mann, Douglas L (2014) Colchicine and the failing heart: a ""FINER"" anti-inflammatory agent? JACC Heart Fail 2:138-40 |
| Burns, Alan R; Phillips, Sharon C; Sokoya, Elke M (2012) Pannexin protein expression in the rat middle cerebral artery. J Vasc Res 49:101-10 |
| Mann, Douglas L (2012) Sphingosine 1-phosphate as a therapeutic target in heart failure: more questions than answers. Circulation 125:2692-4 |
| Hartley, Craig J; Reddy, Anilkumar K; Madala, Sridhar et al. (2011) Doppler velocity measurements from large and small arteries of mice. Am J Physiol Heart Circ Physiol 301:H269-78 |
| Hartley, Craig J; Reddy, Anilkumar K; Madala, Sridhar et al. (2010) Feasibility of dual Doppler velocity measurements to estimate volume pulsations of an arterial segment. Ultrasound Med Biol 36:1169-75 |
| Haudek, Sandra B; Gupta, Damon; Dewald, Oliver et al. (2009) Rho kinase-1 mediates cardiac fibrosis by regulating fibroblast precursor cell differentiation. Cardiovasc Res 83:511-8 |
| Reddy, Anilkumar K; Namiranian, Khodidad; Lloyd, Eric E et al. (2009) Effect of isoflurane on aortic impedance in mice. Conf Proc IEEE Eng Med Biol Soc 2009:1104-5 |
| Divakaran, Vijay; Adrogue, Julia; Ishiyama, Masakuni et al. (2009) Adaptive and maladptive effects of SMAD3 signaling in the adult heart after hemodynamic pressure overloading. Circ Heart Fail 2:633-42 |
| Wu, Huaizhu; Gower, R Michael; Wang, Hong et al. (2009) Functional role of CD11c+ monocytes in atherogenesis associated with hypercholesterolemia. Circulation 119:2708-17 |
| Liu, Xiuping; Zuo, Yumei; Zhang, Weina et al. (2009) Expression of interleukin-15 and its receptor on the surface of stimulated human umbilical vein endothelial cells. J Huazhong Univ Sci Technolog Med Sci 29:527-34 |
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