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Peculiarities of biochemical and functional disorders in cardiovascular system in type 2 diabetes mellitus under estrogen deficiency (experimental study)

Work number - M 20 FILED

Presented byState Institution “V. Danilevsky Institute for Endocrine Pathology Problems of the NAMS of Ukraine”.

Author: Kiprych T. V.

The aim of the researchwas to study effects of endogenous and exogenous estrogen on biochemical and functional disorders in cardiovascular system in type 2 diabetes.

It was establishedthat estrogen deficiency enhances negative effect of high calory diet on progression of insulin resistance, but doesn’t influence the development and severity of dyslipidemia in female diabetic rats. Hypoestrogenic state in type 2 diabetes was found to increase oxidative stress in cardiomyocyte mitochondria through inhibition of antioxidant enzymes and decreaseinsome components ofrespiration chain. At the same time endothelial NO‑synthaseand heme oxygenase activity appeared to be independentofendogenous estrogen in diabetic rats.Increased levels of serum tumor necrosis factor‑αand plasma fibrinogen and also disturbances of ventricular myocardial depolarization and repolarization processes were observed in non-diabetic ovariectomized rats, whileaccentuated impairment of functional state of cardiovascular system (sinus tachycardia, systolic and diastolic dysfunction) was detected in diabetic animalswith estrogen deficiency compared to those with intact ovaries.It was shown that per os administration of selective estrogen receptor modulator PE0607 to ovariectomized diabetic rats as well as 17β‑estradiol resulted in lowering of hypertriglyceridemia and total lipids in liver, restricted oxidative imbalance in serum, prevented significantly cardiomyocyte mitochondrial dysfunction, increased endothelial NO‑synthase activity, attenuated inflammation intensity and contributed largely to maintenance of normal heart rate, intraventricular impulse conduction and ventricular repolarization process, but in contrast to 17β‑estradiol itdidn’t affect the uterus mass.

Scientific and practical value.The results of the study enhance understanding of pathogenesisofcardiovasculardiseasein diabetes mellitus considering changes in heart mitochondria functional state and vessel wall biochemical disturbances depending on the estrogen level. The study could contribute to a development and optimization of the novel gender-specific prevention and treatment strategies incardiovascular therapy of postmenopausal women with type 2 diabetes. Protective cardiometabolic effects of the compound PE0607 found in the diabetic ovariectomized rats indicate the need of further investigation of the PE0607 as a potential sex-specific agent capable to impair cardiovascular risk in females with type 2 diabetes under estrogen deficiency.

Comparison with world analogues: the study corresponds to the world level.

Incorporations by the study:patent for a utility model, scientific publications, conference reports; educational and scientific work of the Pharmacognosy, Pharmacology and Botany Department of the Zaporizhzhia State Medical University.

Economic effect from incorporationsis being determined.

Publicationsby the study include 15 papers, among them – 6 articles in scientific journals indexedininternational scientometric databases, 1 patent of Ukraine for a utility model, 8 abstracts in materials of scientific international conferences. Total number of references to co-authors publications according to Google Scholar– 129, h‑index – 6, according to SCOPUS– 11, h‑index – 3.By the materials of the study a PhD thesis on biological sciences was defended (specialty 14.01.14 “Endocrinology”).