Education and Post-Graduate Training

Research Interests

My research focuses on the physiological and pathophysiological regulation of coronary 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 coronary 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 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, 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 coronary flow regulation, these 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 coronary microvascular network under normal and disease states.

Selected Publications

Zhang C, Hein TW, Wang W, Ren Y, Shipley RD, and Kuo L. Activation of JNK and xanthine oxidase by TNF-alpha impairs nitric oxide-mediated dilation of coronary arterioles. J Mol Cell Cardiol 40:247-257, 2006. PMID: 16413574

Zhang C, Wang W, Kuo L, Michael L, Bagby G, and Chilian WM. TNF-α contributes to endothelial dysfunction in ischemia/reperfusion injury. Arterioscler Thromb Vasc Biol 26:475-480, 2006. PMID: 16385082

Nagaoka T, Takahashi A, Sato E, Izumi N, Hein TW, Kuo L, and Yoshida A. Effect of systemic administration of statin on retinal circulation.  Arch Ophthalmol 124:665-670, 2006. PMID: 18776862

Rosa RH, Jr, Hein TW, Yuan Z, Xu W, Pechal MI, Geraets RL, Newman JM, and Kuo L. Brimonidine evokes heterogeneous vasomotor response of retinal arterioles: Diminished nitric oxide-mediated vasodilation when size goes small. Am J Physiol Heart Circ Physiol 291:H231-H238, 2006. PMID: 16489103

Thengchaisri N, Hein TW, Wang W, Xu X, Li Z, Fossum TW, and Kuo L. Upregulation of arginase by hydrogen peroxide impairs endothelium-dependent nitric oxide-mediated dilation of coronary arterioles. Arterioscler Thromb Vasc Biol 26:2035-2042, 2006. PMID: 16794224

Nagaoka T, Hein TW, Yoshida A, and Kuo L. Simvastatin elicits dilation of isolated porcine retinal arterioles: Role of nitric oxide and mevalonate-rho kinase pathways. Invest Ophthalmol Vis Sci 48:825-832, 2007. PMID: 17251484

Nagaoka T, Hein TW, Yoshida A, and Kuo L. Resveratrol, a component of red wine, elicits dilation of isolated porcine retinal arterioles: Role of nitric oxide and potassium channels.  Invest Ophthalmol Vis Sci 48:4232-4239, 2007. PMID: 17724212

Thengchaisri N, Shipley R, Ren Y, Parker J, and Kuo L. Exercise training restores coronary arteriolar dilation to NOS activation distal to coronary artery occlusion: Role of hydrogen peroxide. Arterioscler Thromb Vasc Biol 27:791-798, 2007. PMID: 17234725

Yuan Z, Hein TW, Rosa RH Jr, and Kuo L. Sildenafil (Viagra®) evokes retinal arteriolar dilation: Dual pathways via NOS activation and phosphodiesterase inhibition. Invest Ophthalmol Vis Sci 49: 720-725, 2008. PMID: 18235020

Nagaoka T, Kuo L, Ren Y, Yoshida A, and Hein TW. C-Reactive protein inhibits endothelium-dependent nitric oxide-mediated dilation of retinal arterioles via enhanced superoxide production. Invest Ophthalmol Vis Sci 49:2053-2060, 2008. PMID: 18436840