Identification of the molecular pathways and microRNAs involved in autophagy deficiency in vascular smooth muscle cells.

Atherosclerotic plaque rupture remains the leading cause of acute cardiovascular syndromes and death. Therefore, additional therapy that reduces atherosclerosis or prevents plaque rupture is needed. Autophagy is a cellular housekeeping mechanism that under certain conditions induces cell death. Recent findings indicate that autophagy deficiency has a major impact on destabilization of advanced atherosclerotic plaques. In the current project we will focus on the role of autophagy in vascular smooth muscle cells (VSMCs), since these cells are key players in the development of atherosclerosis. Moreover, our research group discovered that defective autophagy in VSMCs leads to accelerated atherosclerosis. Thus, inducing autophagy seems a plausible therapeutic strategy to treat cardiovascular disease. However, none of the drugs that were specifically designed to modulate autophagy are currently approved for human use. These compounds often show low specificity for their molecular target and cell type, thereby activating autophagy at the whole-body level. Since autophagy induction can aggravate certain pathologies, such as cancer, these low-specific drugs impose health risks. Therefore, the current research project aims to overcome these risks and specificity problems by identifying the downstream molecular pathways and microRNAs involved in the harmful effects of autophagy deficiency in VSMCs. For this purpose, the mRNA and microRNA profile of autophagy deficient VSMCs will be analysed via next generation sequencing. As a result, we might reveal new drug targets with enhanced cell type specificity. Eventually, the current proposal can lead to novel anti-atherosclerotic therapies targeting the cellular pathways downstream of autophagy in VSMCs, which is more selective than directly modulating the autophagic process itself.

Keywords:AUTOPHAGY, MICRO RNA, CARDIOVASCULAR SYSTEM, RNA SEQUENCING

Disciplines:Cardiac and vascular medicine, Vascular diseases, Medical transcriptomics