Hypertension is a complex disorder that involves multiple organ systems. Even though the role of immune cells (e.g., macrophages and T lymphocytes) is well accepted in hypertension, the underlying mechanisms are not completely understood. Our major hypothesis is that immune response in hypertension depends on a continuous interaction between immune-activated vascular cells, innate and adaptive immunity. Survival is very important for vascular cells in hypertension. We recently confirmed the pathogenic role for Axl, a receptor tyrosine kinase, on vascular dysfunction in the late phase of salt-sensitive hypertension. Axl-dependent pathways protect hypertensive vasculature from apoptosis. Preliminary data support our working hypothesis that Axl is a key regulator of the immune response in hypertension. We propose three specific aims to test the hypothesis and dissect mechanisms by which Axl regulates the immune response in hypertension. First, we will determine Axl-dependent effects on modulation of immune activation of vascular cells in hypertension. Second, we will identify innate immune cell types that are engaged in Axl-dependent vascular dysfunction in hypertension. Third, we will investigate the regulatory role of Axl in adaptive immunity (CD4 T lymphocytes) that maintains vascular dysfunction in hypertension. Our studies will provide new insights into the pathological mechanisms that regulate vascular dysfunction in hypertension. In particular, we will refine the current concept of the immune response in hypertension and emphasize the importance of retention (via survival) of immune cells in the artery wall at the later phases of hypertension. Finally, Axl-dependent molecular mechanisms can offer a novel therapeutic target for the treatment of hypertension.
This proposal will refine the current concept of vascular dysfunction in hypertension and emphasize the importance of the immune mechanisms in later phases of hypertension. These data will set a strong base for development of original diagnostic tools and/or therapeutic target(s) to treat hypertension.
| Dugbartey, George J; Bouma, Hjalmar R; Lobb, Ian et al. (2016) Hydrogen sulfide: A novel nephroprotectant against cisplatin-induced renal toxicity. Nitric Oxide 57:15-20 |
| Batchu, N; Hughson, Angie; Wadosky, Kristine M et al. (2016) Role of Axl in T-Lymphocyte Survival in Salt-Dependent Hypertension. Arterioscler Thromb Vasc Biol 36:1638-1646 |
| Batchu, Sri N; Xia, Jixiang; Ko, Kyung Ae et al. (2015) Axl modulates immune activation of smooth muscle cells in vein graft remodeling. Am J Physiol Heart Circ Physiol 309:H1048-58 |
| Batchu, Sri N; Smolock, Elaine M; Dyachenko, Igor A et al. (2015) Autonomic dysfunction determines stress-induced cardiovascular and immune complications in mice. J Am Heart Assoc 4: |
| Smolock, Elaine M; Burke, Ryan M; Wang, Chenjing et al. (2014) Intima modifier locus 2 controls endothelial cell activation and vascular permeability. Physiol Genomics 46:624-33 |
| Batchu, Sri N; Hughson, Angie; Gerloff, Janice et al. (2013) Role of Axl in early kidney inflammation and progression of salt-dependent hypertension. Hypertension 62:302-9 |
| Korshunov, Vyacheslav A (2012) Axl-dependent signalling: a clinical update. Clin Sci (Lond) 122:361-8 |
| Ghazalpour, Anatole; Rau, Christoph D; Farber, Charles R et al. (2012) Hybrid mouse diversity panel: a panel of inbred mouse strains suitable for analysis of complex genetic traits. Mamm Genome 23:680-92 |
| Smolock, Elaine M; Ilyushkina, Irina A; Ghazalpour, Anatole et al. (2012) Genetic locus on mouse chromosome 7 controls elevated heart rate. Physiol Genomics 44:689-98 |
| Batchu, Sri N; Korshunov, Vyacheslav A (2012) Novel tyrosine kinase signaling pathways: implications in vascular remodeling. Curr Opin Nephrol Hypertens 21:122-7 |
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