Director, Physiological Genomic Core Laboratory
BRB & MSTF
Chen L, Zadi ZH, Zhang J, Scharf SM, Pae EK. Intermittent hypoxia in utero damages postnatal growth and cardiovascular function in rats. J Appl Physiol (1985). 2018 Apr 1;124(4):821-830. doi: 10.1152/japplphysiol.01066.2016. Epub 2017 Dec 14. PMID: 29357521
Thompson LP, Chen L, Polster BM, Pinkas G, Song H. Prenatal hypoxia impairs cardiac mitochondrial and ventricular function in guinea pig offspring in a sex-related manner. Am J Physiol Regul Integr Comp Physiol. 2018 Oct 26. doi: 10.1152/ajpregu.00224.2018. [Epub ahead of print] PMID: 30365351
Zhang J, Wang Y, Chen L, Wier WG, Blaustein MP. Na/Ca exchanger overexpression in smooth muscle augments cytosolic Ca2+ in femoral arteries of living mice. Am J Physiol Heart Circ Physiol. 2018 Nov 21. doi: 10.1152/ajpheart.00185.2018. [Epub ahead of print] PMID: 30461304
Wang W, Zhang D, Yang R, Xia W, Qian K, Shi Z, Brown R, Zhou H, Xi Y, Shi L, Chen L, Xu F, Sun X, Zhu D, Gong DW. Hepatic and cardiac beneficial effects of a long-acting Fc-apelin fusion protein in diet-induced obese mice. Diabetes Metab Res Rev. 2018 Jul;34(5):e2997. doi: 10.1002/dmrr.2997. Epub 2018 Mar 25. PMID: 29577579
Blaustein MP, Chen L, Hamlyn JM, Leenen FH, Lingrel JB, Wier WG, Zhang J. Pivotal role of α2 Na+ pumps and their high affinity ouabain binding site in cardiovascular health and disease. The Journal of physiology. 2016. doi: 10.1113/JP272419. PMID: 27350568
Chen L, Song H, Wang Y, Lee JC, Kotlikoff MI, Pritchard TJ, Paul RJ, Zhang J, Blaustein MP. Arterial α2-Na+ pump expression influences blood pressure: lessons from novel, genetically engineered smooth muscle-specific α2 mice. American journal of physiology. Heart and circulatory physiology. 2015; 309(5):H958-68. PMCID: PMC4591399
Wang Y, Chen L, Wier WG, Zhang J. Intravital Förster resonance energy transfer imaging reveals elevated [Ca2+]i and enhanced sympathetic tone in femoral arteries of angiotensin II-infused hypertensive biosensor mice. The Journal of physiology. 2013; 591(21):5321-36. PMCID: PMC3936370
Chen L, Zhang J, Hu X, Philipson KD, Scharf SM. The Na+/Ca2+ exchanger-1 mediates left ventricular dysfunction in mice with chronic intermittent hypoxia. Journal of applied physiology (Bethesda, Md. : 1985). 2010; 109(6):1675-85. PMCID: PMC3006405
Scharf SM, Chen L, Slamowitz D, Rao PS. Effects of continuous positive airway pressure on cardiac output and plasma norepinephrine in sedated pigs. J Crit Care. 1996;11(2):57-64.
Cohen RI, Chen L, Scharf SM. The effects of high dose NG-nitro-L-arginine-methyl ester on myocardial blood flow and left ventricular function in dogs. J Crit Care. 1996;11(4):206-13.
Chen L, Scharf SM. Comparative hemodynamic effects of periodic obstructive and simulated central apneas in sedated pigs. J Appl Physiol. 1997;83(2):485-94.
Tarasiuk A, Chen L, Scharf SM. Effects of periodic obstructive apnoeas on superior and inferior venous return in dogs. Acta Physiol Scand. 1997;161(2):187-94.
Sofer S, Cohen R, Shapir Y, Chen L, Colon A, Scharf SM. Scorpion venom leads to gastrointestinal ischemia despite increased oxygen delivery in pigs. Crit Care Med. 1997;25(5):834-40.
Chen L, Sica AL, Greenberg H, Scharf SM. Role of hypoxemia and hypercapnia in acute cardiovascular response to periodic apneas in sedated pigs. Respir Physiol. 1998;111(3):257-69.
Chen L, Scharf SM. Systemic and myocardial hemodynamics during periodic obstructive apneas in sedated pigs. J Appl Physiol. 1998;84(4):1289-98.
Cohen RI, Shapir Y, Chen L, Scharf SM. Right ventricular overload causes the decrease in cardiac output after nitric oxide synthesis inhibition in endotoxemia. Crit Care Med. 1998;26(4):738-47.
Slamowitz D, Chen L, Scharf SM. Effects of vagotomy on cardiovascular response to periodic apneas in sedated pigs. J Appl Physiol. 1999;86(6):1890-6.
Chen L, Sica AL, Scharf SM. Mechanisms of acute cardiovascular response to periodic apneas in sedated pigs. J Appl Physiol. 1999;86(4):1236-46.
Chen L, Shi Q, Scharf SM. Hemodynamic effects of periodic obstructive apneas in sedated pigs with congestive heart failure. J Appl Physiol. 2000;88(3):1051-60.
Chen L, Scharf SM. Effects of aortic nerve on hemodynamic response to obstructive apnea in sedated pigs. J Appl Physiol. 2000;89(4):1455-61.
Chen L, Gan XT, Haist JV, Feng Q, Lu X, Chakrabarti S, Karmazyn M. Attenuation of compensatory right ventricular hypertrophy and heart failure following monocrotaline-induced pulmonary vascular injury by the Na+-H+ exchange inhibitor cariporide. J Pharmacol Exp Ther. 2001;298(2):469-76.
Rojas A, Chen L, Bartlett RH, Arenas JD. Assessment of liver function during extracorporeal membrane oxygenation in the non-heart beating donor swine. Transplant Proc 2004;36 (5):1268-70
Chen L, Chen CX, Gan XT, Beier N, Scholz W, Karmazyn M. Inhibition and reversal of myocardial infarction-induced hypertrophy and heart failure by NHE-1 inhibition. Am J Physiol Heart Circ Physiol. 2004;286(1):H381-7.
Chen L, Einbinder E, Zhang Q, Balke CW, Hasday J, Scharf SM. Oxidative Stress and Left Ventricular Function with Chronic Intermittent Hypoxia in Rats. Am J Respir Crit Care Med. 2005 Oct 1;172(7):915-20. Epub 2005 Jun 23.
Zhang J, Lee MY, Cavalli M, Chen L, Berra-Romani R, Balke CW, Bianchi G, Ferrari P, Iwamoto T, Lingrel JB, Matteson DR, Philipson KD, Wier WG, Blaustein MP. Sodium pump alpha2 subunits control arterial myogenic tone and blood pressure in mice. J Physiol. 2005; 569: 243-56.
Blaustein MP, Zhang J, Chen L, and Hamilton BP. How does salt retention raise blood pressure? Am J Physiol Regul Intergr Comp Physiol (invited review) 2006; 290(3):R514-23.
Sharf SM, Chen L, Greenburg H, O’Donnel CP (2001). Cardiovascular response to obstructive apneas: Lessions from animal models. In: Scharf SM, Pinsky M, Magdar S (eds). Respiratory-Circulatory Interactions in Health and Disease ( bv P613-640.
Chen L (1992). Anticholinergic Drugs. In: Wang S, Ye Y, Luo W (eds.) Bronchial Asthma: Trends in pathophysiology and Treatment (in Chinese). Sandong Scientific and Technological Press. P25-28.
1) Pathogenesis of Cardiac Dysfunction of Obstructive Sleep Apnea
Obstructive sleep apnea/hypopnea syndrome (OSA) affects about 4-6% of males and 2-4% of females in mid-aged population. OSA increases cardiovascular morbidity and mortality due to hypertension, ischemic heart disease, heart failure and stroke. Chronic intermittent hypoxia (CIH), which results from the repetitive episodes of upper airway occlusion during sleep, is important for the cardiovascular sequelae of OSA. Indeed, rats exposed to CIH develop hypertension, ventricular hypertrophy and dysfunction. Recently, we observed an upregulation of myocardial Na+/H+ exchanger-1 (NHE1) in CIH rats and mice. NHE1 regulates cellular pH and Na+ in physiological condition and may be involved in cardiac injury during ischemia and reperfusion injury. We are currently examining the role of NHE1 in cardiac dysfunction following CIH. Multidisciplinary approaches are used, including conscious blood pressure and cardiac output, echocardiography, contractile function of isolated cells, molecular imaging, and genetic modified mice. If NHE1 plays a role in the pathogenesis of cardiac dysfunction, further study on effort of NHE1 inhibition may lead to a novel adjunct therapy for OSA.
2) Mechanisms of Cardiac Dysfunction Following Brain Death
The lifetime risk of developing heart failure is 1 in 5 for men and women. Only heart transplantation offers a meaningful long-term survival for late-stage heart failure, about 50% at 10 years. While estimated 100,000 patients in the United States might benefit from the surgery, however, the procedures are limited to 2,200 annually because of lack of viable hearts donated by brain-dead patients. As clinicians observed a long time ago, hearts can remain viable for only a short period of time following brain death. Using the rat model of brain death, we explore several putative mechanisms, such as NHE1, in initiation of cardiac dysfunction following brain death. Our long-term goal is to develop novel strategies for treatment of the organ donors and/or the donor hearts, in order to improve the availability and quality of donor hearts for transplantation.