Sunday 29 September is World Heart Day, a vital and worldwide initiative dedicated to raising awareness of cardiovascular health. Cardiovascular diseases remain the leading cause of mortality worldwide. A good reason to give extra thought to the importance of research in improving cardiovascular health. That is why we will highlight some of the important research projects from Amsterdam Cardiovascular Sciences (ACS) during this week. Today, we are proud to highlight the fourth and final project this week, which focusses on microvascular ageing and heart failure with preserved ejection function.
Heart failure in the ageing population
Ageing is an important risk for cardiovascular disease in the elderly. The ageing population and higher life expectancy comes with the accumulation of multiple co-morbidities, which in turn promote the development of cardiovascular disease. Specifically, heart failure is the main cause of death among the elderly, leads to increased hospitalization rates and a decreased quality of life.
Heart failure with preserved ejection fraction
The main type of heart failure that is seen in the elderly is heart failure with preserved ejection fraction (HFpEF). HFpEF can be characterized by impaired relaxation or diastolic function of the heart. Unfortunately, there are limited treatment options for HFpEF, which is attributed to the remaining lack of our understanding on the pathophysiology. The goal of prof. Reinier Boon and his colleagues is to better understand this disease in order to develop more effective treatment options for patients with HFpEF in the future. Since endothelial dysfunction becomes more prominent with ageing, the project focuses on the possible role of microvascular endothelial dysfunction in the heart in the diastolic impairment in HFpEF.
LncRNAs potentially drive pathophysiology
To study endothelial function, Boon and colleagues focus on long-non coding RNA’s (lncRNA) and the effect on the cross-talk between endothelial cells and cardiomyocytes. Amongst others, they have discovered the lncRNA’s IRENE and SARRAH. IRENE was found enriched in endothelial cells and showed a protective role. Unpublished data show that IRENE is reduced in HFpEF patients. The loss-of-function of IRENE in endothelial cells impaired endothelial-enhancement of cardiac muscle contractility. The gain-of-function of IRENE however rescued the beneficial effects. This suggests a potential role of IRENE as a novel therapeutic target for HFpEF. As for SARRAH, some of the data from previous works indicate a potential role in regulating cardiomyocyte relaxation, which Boon and colleagues are currently investigating. Using overexpression of human SARRAH transcript in a mouse model of ageing-HFpEF (developed in their group), they will evaluate if gain-of-function of this lncRNA can rescue the diastolic function of the heart.
The effect of HFpEF patient serum on endothelial function
An important part of the project is collaboration with clinical departments to obtain patient samples (e.g. serum from patients with HFpEF). Unpublished data show that serum from these patients impaired the endothelial function to boost cardiomyocyte contractility and reduced IRENE expression in endothelial cells. To gain deeper understanding on endothelial transcription changes that occur, RNA sequencing analysis is currently performed. This may point to pathways that are involved in the development of endothelial function in HFpEF and potentially gives further insights into the understanding of the pathophysiology of HFpEF in the future.
