Kathryn Sandberg, PhD
Professor,Division of Nephrology & Hypertension
Departments of Medicine and Physiology
Sex differences in hypertension and associated cardiovascular and renal disease
My laboratory focuses on the molecular mechanisms underlying the sex differences in the incidence and rate of progression of hypertension and associated cardiovascular and renal disease. The incidence and rate of progression of these disease states is higher in men than age-matched women until women reach menopause. After menopause, women rapidly catch up with men. Some of the major risk factors in these disease processes are increased activity of the renin angiotensin system, the presence of testosterone, and estrogen deficiency. My laboratory investigates the gonadal steroid regulation of the renin angiotensin system. We study the gene regulation of angiotensin receptors (AT1 and AT2), which bind angiotensin II, the key effector hormone of the renin angiotensin system. We are investigating how alternative splicing, short open reading frames, RNA binding proteins control angiotensin receptor gene expression at the level of translation and mRNA stability. We also investigate similarly gene regulatory mechanims in other peptide hormone G protein coupled receptors, including corticotropin releasing hormone, neuropeptide Y and vasopressin receptors. Investigating the molecular mechanisms underlying the physiological control of angiotensin receptors will lend insight into how angiotensin receptor expression is altered during aging and pathophysiological states including end-stage renal disease, salt-sensitive hypertension, renovascular hypertension and left ventricular remodeling.
- Sandberg, K. and H. Ji, “Kidney angiotensin receptors and their role in renal pathophysiology,” Sem Neph, 20: 2000.
- Roesch, D., Tian, Y., Zheng, W., Shi, M., Verbalis, J.G. and K. Sandberg, “Estrogen attenuates angiotensin-induced aldosterone secretion in ovariectomized rats,” Endocrinology 141: 4629-4636, 2000.
- Zheng, W., Ji, H., Zsabo, Z., Brown, P.R., and K. Sandberg, “Coordinate regulation of canine glomeruli and adrenal angiotensin receptors by dietary sodium manipulation in dogs,” Kidney Int, 59: 1881-1890, 2001.
- Szabo, Z., Speth, R.C., Brown, P.R., Kerenyi, L., Mathews, W.B., Ravert, H.T., Hilton, J., Finley, P., Dannals, R.F., Zheng, W., Lee, S. and K. Sandberg, “Use of positron emission tomography to study AT1 receptor regulation in vivo,” J Amer Soc Neph, 12: 1350-1358, 2001.
- Lee, S., Kramer, C.M., Mankad, S., Yoo, S-e. and K. Sandberg, “Combined angiotensin converting enzyme inhibition and angiotensin AT1 receptor blockade up-regulates myocardial AT2 receptors in remodeled myocardium post-infarction”, Cardiovascular Research 51:131-139, 2001.
- Wu, Z., Hassan, A., Zheng, W., Verbalis, J.G. and K. Sandberg, “Estradiol-induced decrease in adrenal angiotensin receptor expression requires modulation of angiotensin,” Endocrinology, in press.
- Wu, Z., Maric, C., Roesch, D., Zheng, W., Verbalis, J.G. and K. Sandberg, “Estrogen regulates adrenal angiotensin AT1 receptors by modulating AT1 receptor translation,” Endocrinology, in press.