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Dr. Jacqueline Novak

Jackie Novak

Professor of Biology

B.S., Walsh University; M.S., University of Akron; Ph.D., University of Cincinnati College of Medicine

Walsh University
A Catholic University of Distinction
2020 East Maple Street
North Canton, Ohio44720
United States

Fighting a "Man's Disease" with the Female Hormone Relaxin

Relaxin hormone diagram
Fighting a "Man's Disease" with the Female Hormone Relaxin

Relaxin could be the Key to Fighting Heart Disease in Women

First Federally Funded Grant For Walsh

Dr. Jackie Novak, associate professor of biology, recently discovered that her scientific research and her personal life have something in common - the heart. With the aid of her husband, Dr. Rolando Ramirez, Dr. Novak is conducting a research study on the hormone relaxin that could potentially prevent women from developing cardiovascular heart disease

Historically labeled as a "man's disease", women were often excluded from medical research specific to heart disease. According to the American Heart Association more woman than men will die this year from cardiovascular disease. Though they may develop cardiovascular disease 10 years later in life than men, heart disease is the No. 1 killer of American women, and claims the lives of 1 in 3 women, or 500,000 women a year.

Dr. Jackie Novak is hoping to reverse those statistics and provide a valuable research opportunity for her students at the same time. Through a three-year grant for more than $350,000 from the National Institutes of Health (NIH), Dr. Novak's team will research the effects of the ovarian hormone relaxin in the treatment of post-menopausal coronary artery dysfunction. The NIH award was the first major federally funded grant for Walsh University and for Dr. Novak.

The research funded by the NIH grant and conducted by Dr. Novak and her team is the only national study focusing on relaxin as it relates to coronary function after menopause.

Relaxin which has been referred to as the "forgotten hormone" is a polypeptide hormone belonging to the insulin family and was first discovered in the United States in 1926. Dr. Novak and her husband Dr. Ramirez began their initial studies of relaxin years ago in Pittsburgh at the Magee-Women's Hospital of UPMC.

"We studied the hormone Relaxin in other body systems but never focused specifically on its relation to coronary function," said Dr. Novak. "When the estrogen replacement therapy trial failed around 2002, I began to wonder 'if not estrogen, maybe relaxin.'"

It is commonly known that women have a lower risk of heart disease than men. But as a woman ages, her chance of heart risk increases, an elevated risk that coincides with declining levels of estrogen after menopause. During the 1980s and 1990s medical experts began to advise older women to take estrogen and other hormones to help reduce the risk of heart disease after menopause. Unfortunately, the hoped-for benefits did not materialize and in 2002, a large-scale research study, the Women's Health Initiative (WHI), revealed a slight increase in heart disease, blood clots and strokes in postmenopausal women using hormone therapy.

Relaxin, like estrogen, is produced by the ovaries and also significantly decreases in women after menopause. "I began to wonder if there was a connection with coronary disease. We conducted a pilot study on rats and the results were promising. Results showed that relaxin could be a viable option. An added benefit is that relaxin is not a feminizing hormone like estrogen – so it could also become an option for men. "

Drs. Novak and Ramirez, a faculty member at The University of Akron, will collaborate with a team of senior investigators from major universities in the United States including the University of Florida and the University of Mississippi. The grant will also provide an opportunity for Walsh undergraduate students to join in the research and collaborate with graduate students from The University of Akron.

"This grant will give our students an amazing opportunity to be exposed to research with real world applications," said Dr. Novak, a former Walsh biology student herself and Walsh alum. "Their work will have the potential to save lives. You can't get a more real-world experience than that in my book."

Publications

Folzenlogen, S.L., Novak, J. and Banks, R.O. Mannitol and saline induced changes in cardiorenal actions of endothelin. Proc. Soc. Exptl. Biol. Med. 200:  378-382, 1992.

Novak, J. and Banks, R.O.  Lead and nickel alter the cardiorenal actions of endothelin in the rat. Proc. Soc. Exptl. Biol. Med., 208: 191-198, 1995.

Granger, J., J. Novak, C. Schnackenberg, S. Williams,  G. Reinhart.   Role of renal nerves in mediating the long-term hypertensive and renal effects of nitric oxide synthesis inhibition. Hypertension 27 (2): 613-618, 1995.

Granger, J.,  C. Schnackenberg, J. Novak, B. Tucker, T. Miller, S. Morgan, and S. Kassab. Role of nitric oxide in modulating the long-term renal and hypertensive actions of norepinehrine.  Hypertension 29(2): 205-209,1997.

Novak, J., J.F. Reckelhoff,  L. Bumgarner, K. Cockrell, S.E. Kassab, J.P. Granger.  Reduced sensitivity of the renal circulation to angiotensin II in pregnant rats.  Hypertension 30(2): 580-584, 1997.

Kassab, S., J. Novak,  T. Miller,  K. Kirchner, J.P. Granger.  Role of endothelin in mediating the attentuated renal hemodynamics in Dahl Salt-Sensitive Hypertension.  Hypertension 30(2):682-686, 1997.

Kassab, S., M.T. Miller, R. Hester, J. Novak, J.P. Granger.   Systemic hemodynamics and regional bloodflow during chronic nitric oxide synthesis inhibition in pregnant rats. Hypertension 31(1 pt2): 315-320, 1998

Kassab, S., M.T. Miller, J. Novak, J. Reckelhoff, B. Clower, J.P. Granger. Endothelin-A receptor antagonism attenuates the hypertension and renal injury in Dahl salt-sensitive rats. Hypertension 31(2):397-402, 1998.

Khalil, R.A., J.K. Crews, J. Novak, S. Kassab, J.P. Granger. Enhanced vascular reactivity during inhibition of nitric oxide synthesis in pregnant rats.  Hypertension 31(5):1065-1069, 1998.

Alexander B.T., M.T. Miller, S. Kassab, J. Novak, J.F. Reckelhoff, W.C. Kruckeberg, J.P. Granger. Differential expression of renal nitric oxide synthase isoforms during pregnancy in rats. Hypertension 33(1pt2): 435-9, 1999.

Granger J.P., S. Kassab, J. Novak, J.F. Reckelhoff, B. Tucker, M.T. Miller.  Role of nitric oxide in modulating renal function and arterial pressure during chronic aldosterone excess.  Am. J Physiol. 276(1 Pt 2): R197-202, 1999.

Crew, J.K., J. Novak, J.P. Granger, R.A. Khalil. Stimulated mechanisms of Ca2+ entry into vascular smooth muscle during NO synthesis inhibition in pregnant rats. Am. J Physiol. 276(2 pt2): R530-8, 1999.

Conrad, K.P., L.A. Danielson, J. Novak,  L.J. Kerchner, O.D. Sherwood,  R.E. Gandley, R. J. Ramirez, and P.A. Moalli.. Is relaxin is the elusive renal vasodilator of pregnancy. In: Relaxin 200 3rd International Conference on Relaxin & Related Peptides. Tregear, G.W., Ivell, R., Bathgate, R.A. and Wade, J.D., 2001.

Novak J,  L.A. Danielson, L.S. Kerchner, O.D. Sherwood,  R. J. Ramirez, P.A. Moalli, and K.P. Conrad.  Relaxin is the  elusive renal vasodilator of pregnancy.  J. Clin. Invest., 107: 1469-1475, 2001.

Conrad, K.P., R.W. Powers, A.K. Davis and J. Novak. Citrulline is not the major product using the standard NOS activity assay on renal cortical homogenates. Am. J. Physiol. 282:R303-R310, 2002. 

Ramirez, R.J., J. Novak, R.E. Gandley, T.P. Johnston, M.K. McLaughlin, C.A. Hubel. Endothelial function and myogenic reactivity in small mesenteric arteries of hyperlipidemic pregnant rats. Am. J. Physiol.281: R1330-1337, 2001

J. Novak, R. J.J. Ramirez, R. E. Gandley, O. D. Sherwood and K. P. Conrad. Myogenic reactivity is reduced in small renal arteries isolated from relaxin-treated rats. Am. J. Physiol., 283:R349-R355, 2002.

Jeyab, A., *J.Novak*. L.A. Danielson*, L.J. Kerchner, S.L. Opett, and K.P. Conrad Essential role for vascular gelatinase activity in relaxin-induced renal vasodilation, hyperfiltration and reduced myogenic reactivity of small arteries. Circ Res. 93:1249-1257, 2003. *authors contributed equally to this work.

Novak, J. R. J. Rajakumar, T. M. Miles, and K.P. Conrad. Nitric oxide synthase isoforms in the rat kidney during pregnancy, Journal of Society for Gynecological Investigation 11(5): 280-288, 2004.

Conrad, K.P., D. O. Debrah, J. Novak , L.A. Danielson, and S.G. Shroff. Relaxin modifies systemic, arterial resistance and compliance in conscious, nonpregnant rats. Endocrinology 145:3289-3296, 2004.

Conrad, K.P., J. Novak. Emerging role of relaxin in renal and cardiovascular function. Am J. Physiol (invited review) 287:R250-R261, 2004

Kerchner, L.J., J. Novak, K. Hanley-Yanez, K.D. Doty, and K.P. Conrad. Evidence against the hypothesis that endothelial endothelin B receptor expression is regulated by relaxin and pregnancy.  Endocrinol., Accepted with minor revisions.

Ramirez, R.J.J, C.A. Hubel, J. Novak, J.R. DiCianno, V.K. Kagan, and R.E. Gandley. Moderate ascorbate deficiency increases myogenic tone of arteries from pregnant but not virgin acorbate-dependent rats. Hypertension 2006; 47:1-7, 2006.

Lucitti, J., R. Visconti, J. Novak, B. Keller. Increased arterial load alters aortic structural and functional properties during embryogenesis. Am. J Physiol., in press, 2006.

Debrah, D.O., J. Novak, J.E. Matthews, R.J. Ramirez, S.G. Shroff, K.P. Conrad. Relaxin is essential for systemic vasodilation and increased global arterial compliance during early pregnancy in conscious rats. Endocrinology. 147(11), 2006.

Novak, J., L.J. Parry, J.E. Matthews, L.J. Kerchner, K. Indovina, K. Hanley-Yanez, K.D. Doty, D.O. Debrah, S.G. Shroff, K.P. Conrad. Evidence for local relaxin ligand-receptor expression and function in arteries. FASEB J. 20:2352-2362, 2006.

Jeyabalan, A., J. Novak, K.D. Doty, J. Matthews, M.C. Fisher, L.J. Kerchner, K.P. Conrad. Vascular matrix metalloproteinase-9 mediates the inhibition of myogenic reactivity in small arteries isolated from rats after short-term administration of relaxin. Endocrinology 148(1): 189-197, 2007.

Ramirez RJJ, Matthews JE, Novak J Altered Myogenic Responsiveness in Resistance Sized Mesenteric Arteries after Uterine Perfusion Pressure Reductions in Late Pregnant Rats. Hypertension In Pregnancy. Posted online on September 6, 2010. (doi:10.3109/10641950903322923), 2010.

Reho JJ, Peck JP, Novak J, Ramirez RJ. Hypertension Induced by Episodic Reductions in Uteroplacental Blood Flow in the Gravid Rat. Hypertension in Pregnancy. POSTED ONLINE ON SEPTEMBER 16, 2010. (DOI:10.3109/10641955.2010.507853), 2010.

Jonathan T. McGuane, Leslie A. Danielson, Julianna E. Debrah, J. Peter Rubin, Jacqueline Novak, Kirk P. Conrad. Angiogenic Growth Factors Are New and Essential Players in the Sustained Relaxin Vasodilatory Pathway in Rodents and Humans. Hypertension. 2011; 57: 1151-1160.

Jonathan T. McGuane, Julianna E. Debrah, Laura Sautina, Yagna P. R. Jarajapu, Jacqueline Novak, J. Peter Rubin, Maria B. Grant, Mark Segal and Kirk P. Conrad. Relaxin Induces Rapid Dilation of Rodent Small Renal and Human Subcutaneous Arteries via PI3 Kinase and Nitric Oxide. Endocrinology July 1, 2011 vol. 152 no. 7 2786-2796.

Toot JD, Reho JJ, Novak J, Dunphy G, Ely DE, and Ramirez RJJ. Colony Social Stress Differentially Alters Blood Pressure and Resistance-sized Mesenteric Artery Reactivity in SHR/y and WKY Males. Stress 14,1:33- 41, 2011.

Toot JD, Reho JJ, Novak J, Dunphy G, Ely DE, and Ramirez RJJ. Testosterone Increases Myogenic Reactivity of Second-order Mesenteric Arteries in Both Defective And Normal Androgen Receptor Adult Male Rats. Gender Medicine. 8, 1: 40-52, 2011.

 Reho JJ, Peck JP, Novak J, Ramirez RJJ. Increased myogenic reactivity of uterine arteries from pregnant rats with reduced uterine perfusion pressure. Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health. 2,2: 106-114, 2011.

Toot JD, Reho JJ, Novak J, Ramirez RJJ and Ely DE. Alterations in vasomotor systems and mechanics of resistance-sized mesenteric arteries from SHR and WKY male rats following in vivo testosterone manipulation. Biology of Sex Differences. 3,1, 2012.

Presentations

Poster presentation at the FASEB meeting , 1991

Poster presentation at Experimental Biology Meeting, 1993Poster presentation at Experimental Biology Meeting,1994

Poster presentation at  Experimental  Biology Meeting, 1996

Poster presentation at American Society of Hypertension1996

Poster presentation at Experimental Biology Meeting,1997

Oral presentation at the 12th Scientific Meeting The Inter-American Society of Hypertension, 199

Poster presentation at Experimental Biology Meeting, 1999

Poster presentation at the Society for Gynecological Investigation, 1999

Oral presentation at the Third International Conference on Relaxin and Related Peptides, 2000

Oral presentation at Experimental Biology Meeting, 2001

Poster presentation at Experimental Biology Meeting, 2002

Poster presentation at Society for Gynecological Investigation, 2003

Oral presentation at Experimental Biology Meeting, 2004

Poster presentation at Experimental Biology Meeting, 2004

Oral presentation at the Fourth International Conference on Relaxin and Related Peptides, 2004

Oral presentation at the No-Name meeting, 2004

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