New gender specific insights into myocardial remodelling in human aortic valve stenosis

• Applicant: Dr. Elke Dworatzek
• Subject Area: Cardiology, Angiology
• Term: from 2011 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 195442542

Women with aortic stenosis (AS) undergoing aortic valve replacement show preoperatively more frequently left ventricular (LV) hypertrophy compared to men and exhibit postoperatively a faster regression. In surgical septal biopsies of patients with AS, men showed a stronger induction of profibrotic gene expression (collagen and matrix metalloproteinases) compared to females. A greater amount of fibrosis could be a potential mechanism for decelerated LV hypertrophy regression in males. In isolated rat cardiac fibroblasts 17ß-Estradiol (E2) increased mRNA expression of collagen I and III in male cells and decreased collagen expression in females. These findings suggest a sexspecific regulation in the formation of myocardial fibrosis which may be of clinical relevance. Our main goal is to dissect the underlying molecular mechanisms of sex-differences in LV hypertrophy and regression. Sex-differences of the extracellular matrix regulation will be confirmed on protein and at histological level. Treatment of female and male intra-operative biopsies with the sex hormone E2 will reveal sex-differences in the effect of E2 on collagen expression in human samples. We will target the underlying molecular mechanisms leading to sex-differences in collagen expression by E2 and estrogen receptors (ER). For this purpose, we will identify the involved ER subtypes and determine how their transcriptional activity is modulated by cofactors or phosphorylation in both sexes.

• DFG Programme: Research Grants
• Participating Persons: Dr. Georgi Petrov; Professorin Dr. Vera Regitz-Zagrosek