Dr. Rubin’s research is focused on understanding cellular pathways that regulate cardiovascular function during health and disease states. There are three major projects within the laboratory: 1) How do immune mediators, released during inflammatory conditions (endotoxemia/sepsis, atherosclerosis) cause myocardial and/or vascular failure? Investigations focus on alterations in second messenger system(s) and cellular targets such as potassium and calcium channels. Therapeutic modalities also are probed as a means to identify affected pathways. 2) What are the cellular pathways that mediate vascular hypoxic vasodilation? Matching of blood flow to meet tissue substrate needs is a fundamental property of the vasculature. However, the signals and vascular mechanisms responsible for dilation are unknown. We have targeted three sites for involvement in hypoxic vasodilation, AMP-activated kinase, Akt and voltage-dependent potassium channels. 3) What is the role of sex hormones in modulating cardiovascular function? Specifically, do sex hormones alter expression of voltage-dependent potassium channels in either vascular smooth muscle or the myocardium? Myocardial studies examine both intrinsic (potassium currents of cardiac myocytes) and extrinsic (heart rate variability) control of heart rate. Methodologies include those needed to: 1) measure contraction, Ca2+, and ionic currents of isolated ventricular myocytes; 2) measure intracellular second messenger molecules, their substrates and products (gel electrophoresis ion chromatography, high performance liquid chromatography, gas chromatography and mass spectrometry), 3) in vitro physiology of vascular function and 4) in vivo assessment of heart rate variability. Our animal models include a swine model of sex hormone replacement (estrogen or testosterone), guinea pig and rat models of endotoxemia and genetically modified mouse models lacking components of signaling pathways that regulate cardiovascular function.
Zhong J, Hwang T-C, Adams HR, and Rubin LJ: Reduced L-type calcium current in ventricular myocytes from endotoxemic guinea pigs. Am J Physiol, Heart Circ Physiol, 42/5: H2312-2324. 1997.
Rigby SL, Hofmann PA, Adams HR and Rubin LJ: Endotoxin-induced myocardial dysfunction is not associated with alterations in myofilament Ca2+ sensitivity. Am J Physiol, Heart Circ Physiol, 43: H580-590. 1998.
Jones AW, Rubin LJ and Magliola L: Endothelin-1 sensitivity of porcine coronary arteries is reduced by exercise training and is gender dependent. J Applied Physiol, 87(3): 1172-1177, 1999.
Rubin LJ, Johnson LR, Dodam, JR, Dhalla AK, Magliola,L, Laughlin MH and Jones AW: Selective transport of adenosine into porcine coronary smooth muscle. Am J Physiol, 279: H1397-H1410, 2000.
Dhalla, AK, Dodam, J, Jones, AW, and Rubin, LJ: Characterization of an NBTI-sensitive nucleoside transporter in vascular smooth muscle. J. Molecular and Cellular Cardiology 33/6, 1143-1152, 2001.
Laughlin, MH, Rubin, LJ, Rush, JWE, Price, EM, Schrage, WG, and Woodman, CR. Short-term training increases endothelium-mediated relaxation in conduit coronary arteries, not coronary arterioles. Journal Applied Physiology, 94: 234-244. 2003.
Costello, MF, Otto, CM, and Rubin, LJ. The role of tumor necrosis factor-a (TNF-a) and the sphingosine pathway in sepsis-induced myocardial failure. J. Vet. Emerg. Crit. Care, 13(1):25-34. 2003.
Franke,R, Yang,Y, Rubin, LJ, Magliola, L, and Jones, AW. High fat diet alters adenosine sensitivity and K-currents in porcine coronary arteries. Journal of Cardiovascular Pharmacology. 43/4: 495-503. 2004.
Bowles,DK, Maddali,KK, Ganjam,V.K., Rubin,LJ, Tharp,DL, Turk, JR, Heaps,CL. Endogenous testosterone increases L-type Ca2+ channel expression in porcine coronary smooth muscle. Am. J. Physiol: 287: H2091-2098. 2004.
Rubin, LJ, Magliola, L, Feng, X, Jones, AW, Hale, CC. Metabolic activation of AMP-kinase in vascular smooth muscle. Journal of Applied Physiology 98, In Press, 2005.