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Nikolai Zhelev

Nikolai Zhelev

Abertay University, UK

Title: Novel stem-cell-based approaches in the development of cyclin-dependent kinase inhibitors as new therapeutics in cardiology

Biography

Biography: Nikolai Zhelev

Abstract

Cardiovascular diseases (CVD) remain the leading cause of morbidity and mortality worldwide, resulting in more than 17.5rnmillion global deaths per annum. Current therapeutic treatments are limited in effectiveness, and research in the field of cardiology is ongoing to address this alarming health issue. The lack of physiologically relevant preclinical models has been identifiedrnas the underlying cause of inefficacy where preclinical trials of therapies have often looked to animal models. As a consequence,rninnovative research into the use of stem cells as model systems in cardiovascular drug discovery is underway. Human embryonicrnstem cells (hESCs) hold great promise in bringing new and effective cardiovascular treatments to the market through providingrnan improved testing platform for pre-clinical drug screening. Cardiomyocytes derived from hESCs aim to overcome the lack ofrnphysiologically relevant preclinical models for toxicology testing by providing a novel system that is scalable, reproducible andrnfrom an inexhaustible source. Recent research carried out at Abertay University in Dundee, has established a novel human ‘miniheart’rncell-based assay, which involves inducing cardiac hypertrophy within hESC-derived cardiomyocyte clusters using growthrnfactors including Angiotensin II and Endothelin-1. This allows for assessment of the therapeutic potential of novel compounds inrntreating the hypertrophic condition, and avoids the contentious use of animal models. The effectiveness of cyclin-dependent kinasern(CDK) inhibitors as drug candidates for therapeutic intervention in cardiac hypertrophy is currently under investigation. Our datarnhas demonstrated that the CDK inhibiting compounds are successful in preventing the induction of cardiac hypertrophy through inhibition of CDK9