Lih Kuo, PhD
Associate Department Head - Temple Campus
Director, Ophthalmic Vascular Research Program
Education and Post-Graduate Training
BS, Biology, 1979, Tunghai University (Taiwan)
MS, Physiology, 1983, National Taiwan University
PhD, Physiology, 1987, Medical College of Virginia
My research focuses on the physiological and pathophysiological regulation of coronary and retinal microcirculation. In the circulatory system, the amount of blood delivered to each tissue can be regulated by the activity of arterial microvessels (<100 µm in diameter). Changes in vascular tone, i.e., constriction or dilation of these microvessels, will decrease or increase blood supply to the tissue, respectively. However, the mechanisms involved in the regulation of vascular tone are not completely understood. Our current research focuses on the regulation of microvascular tone by hemodynamic (e.g., pressure and shear stress), metabolic (e.g., adenosine, osmolarity, K+, pH, pO2) and neural (adrenergic receptors) factors. The interplay among these factors and the underlying cellular/subcellular mechanisms in the integrative regulation of coronary and retinal microvascular function are studied. Based on this fundamental information, the pathophysiological disturbances of coronary microvascular function during disease states (e.g., atherosclerosis, septic shock, hypertension, diabetes, and ischemia-reperfusion injury) are investigated using various techniques and approaches including 1) cell culture and isolated vessel for assessing cellular and vascular function, 2) molecular analysis of protein and gene expression, 3) biochemical and pharmacological determination of signaling pathways, 4) fluorescence microscopy and immunohistochemistry for calcium signaling and protein localization, and 5) determination of gene activation and vascular remodeling. To have an integrative view on the flow regulation, this basic information are reconstructed using mathematical model and computer simulation technology. This research provides a basic foundation critical to our understanding of blood flow regulation in the microvascular network under normal and disease states.
- Hein TW, Xu W, Ren Y, Kuo L. Cellular signaling pathways mediating dilation of porcine pial arterioles to adenosine A2Areceptor activation. Cardiovasc Res 99: 156-163, 2013.
- Kuo L and Hein TW. Vasomotor regulation of coronary microcirculation by oxidative Stress: Role of Arginase. Front Immunol 4 (237): 1-12, 2013.
- Hein TW, Qamirani E, Ren Y, Xu X, and Kuo L. Selective activation of LOX-1 mediates C-reactive protein evoked endothelial vasomotor dysfunction in coronary arterioles. Circ Res 114: 92-100, 2014.
- Hein TW, Rosa RH Jr, Ren Y, Xu W, and Kuo L. VEGF receptor-2-linked PI3K/Calpain/SIRT1 activation mediates retinal arteriolar dilations to VEGF and shear stress. Invest Ophthalmol Vis Sci 56:5381-5389, 2015.
- Thengchaisri N, Hein TW, Ren Y, and Kuo L Endothelin-1 impairs coronary arteriolar dilation: Role of p38 kinase-mediated superoxide production from NADPH Oxidase. J Mol Cell Cardiol 86:75-84, 2015.
- Tsai SH, Lu G, Xu X, Ren Y, Hein TW, Kuo L. Enhanced endothelin-1/Rho-kinase signalling and coronary microvascular dysfunction in hypertensive myocardial hypertrophy. Cardiovasc Res. 2017 Sep 1;113(11):1329-1337. doi: 10.1093/cvr/cvx103. PMID: 28575410; PMCID: PMC5852513
- Tsai SH, Xie W, Zhao M, Rosa RH Jr, Hein TW, Kuo L. Alterations of Ocular Hemodynamics Impair Ophthalmic Vascular and Neuroretinal Function. Am J Pathol. 2018 Mar;188(3):818-827. doi: 10.1016/j.ajpath.2017.11.015. PMID: 29309745; PMCID: PMC5840493
- Zhao M, Xie W, Tsai SH, Hein TW, Rocke BA, Kuo L, Rosa RH Jr. Intravitreal Stanniocalcin-1 Enhances New Blood Vessel Growth in a Rat Model of Laser-Induced Choroidal Neovascularization. Invest Ophthalmol Vis Sci. 2018 Feb 1;59(2):1125-1133. doi: 10.1167/iovs.17-23083. PMID: 29490350; PMCID: PMC5830987
- Chen YL, Ren Y, Xu W, Rosa RH Jr, Kuo L, Hein TW. Constriction of Retinal Venules to Endothelin-1: Obligatory Roles of ETA Receptors, Extracellular Calcium Entry, and Rho Kinase. Invest Ophthalmol Vis Sci. 2018 Oct 1;59(12):5167-5175. doi: 10.1167/iovs.18-25369. PMID: 30372743; PMCID: PMC6203175