The role of the micro vasculature in cardiac ageing and disease

Alterations and functional impairment of the cardiac microvasculature are associated to heart failure and cardiac disease. Ageing is a major risk factor in cardiovascular disease (CVD) and critically affects cardiac function and structure. Although cardiac ageing has been well studied in cardiomyocytes, endothelial cells and fibroblasts, the molecular and cellular alterations in cardiac pericytes during ageing are largely unknown. Ageing reduced pericyte area con capillary coverage in the murine heart. Single nucleus RNA sequencing analysis further revealed that the expression of Rgs5 was reduced in cardiac pericytes from aged mice. In vivo and in vitro studies showed that the deletion of RGS5 impaired cardiac function, fibrosis, and induced morphological changes and a pro-fibrotic gene expression signature in pericytes and the paracrine activation of fibroblasts in a TGFβ2-dependent mechanism. Furthermore, the extracellular matrix is the most regulated component in the aged heart. Our results have further shown that decorin, a small leucine rich proteoglycan that is secreted into the extracellular matrix and upregulated in aged endothelial cells, contributes to the age related structural and functional dysfunction of the heart by inducing a pro-inflammatory environment in the myocardial microvasculature, a hallmark of cardiac ageing.

Guillermo Luxan: 

I did my PhD in the Spanish National Center for Cardiovascular Research (CNIC) in Madrid. Under the supervision of Dr. José Luis de la Pompa I studied the role of the NOTCH pathway regulator Mind bomb1 in heart development. In particular, we identified 2 new mutations in MIB1 that cause left ventricular non-compaction cardiomyopathy (LVNC). Then, I move to the Max Planck Institute for Molecular Biomedicine in Münster. In the laboratory of Dr. Ralf Adams, I studied the cardiac micro vasculature. We showed that deletion of EphB4 or its ligand ephrin-B2 in endothelial cells induces a phenotype that resembles the human dilated cardiomyopathy (DCM). Now, in the Institute of Cardiovascular Regeneration in Frankfurt, I am studying the role of the cardiac micro vasculature in ageing and chronic heart failure with a special focus on pericytes. Furthermore, we are interested in the inter organ communication and have already shown that post-myocardial infarction heart failure dysregulates the bone vascular niche.