Dr. Barouch’s laboratory is focused on defining the peripheral cardiovascular effects of the adipocytokine leptin, which is a key to the understanding of obesity-related cardiovascular disease. Interestingly, many of the hormonal abnormalities seen in obesity are mimicked in heart failure. The research program will enhance the understanding of metabolic signaling in the heart, including the effects of leptin, exercise, sex hormones, and downstream signaling pathways on metabolism and cardiovascular function. The lab also is working to determine the precise role of the “metabolic” beta-3 adrenergic receptor (ß3AR) in the heart and define the extent of its protective effect in obesity and in heart failure, including its role in maintaining nitric oxide synthase (NOS) coupling. Ultimately, this work will enable the exploration of a possible therapeutic role of ß3AR agonists and re-coupling of NOS in preventing adverse ventricular remodeling in obesity and in heart failure.
Barouch LA, Harrison RW, Skaf MW, Rosas GO, Cappola TP, Kobeissi ZA, Hobai IA, Lemmon CA, Burnett AL, O'Rourke B, Rodriguez ER, Huang PL, Lima JAC, Berkowitz DE, Hare JM. Nitric oxide regulates the heart by spatial confinement of nitric oxide synthase isoforms. Nature. 2002; 416:337-339
Barouch LA, Gao D, Chen L, Miller KL, Xu W, Phan AC, Kittleson MK, Minhas KM, Berkowitz DE, Wei C, Hare JM. Cardiac myocyte apoptosis is associated with increased DNA damage and decreased survival in murine models of obesity. Circulation Research. 2006; 98(1):119-24
Yang R, Sikka G, Larson J, Watts VL, Niu X, Ellis CL, Miller KL, Camara A, Reinke C, Savransky V, Polotsky VY, O'Donnell CP, Berkowitz DE, Barouch LA. Restoring leptin signaling reduces hyperlipidemia and improves vascular stiffness induced by chronic intermittent hypoxia. American J Physiol Heart Circ Physiol. 2011; 300(4):H1467-76
Niu X, Watts VL, Cingolani OH, Sivakumaran V, Leyton-Mange JS, CL, Miller KL, Vandegaer K, Bedja D, Gabrielson KL, Paolocci‎ N, Kass DA, Barouch LA. Cardioprotective Effect of Beta-3 Adrenergic Receptor Agonism: Role of Neuronal Nitric Oxide Synthase. JACC. 2012; 59(22):1979-87
Watts VL, Sepulveda FM, Cingolani OH, Ho AS, Niu X, Kim R, Miller KL, Vandegaer K, Bedja D, Gabrielson KL, Rameau G, O'Rourke B, Kass DA, Barouch LA. Anti-hypertrophic and anti-oxidant effect of beta3-adrenergic stimulation in myocytes requires differential neuronal NOS phosphorylation. J Mol Cell Cardiol. 2013; 62:8-17