Investigation of the mechanisms of heart failure development in Tgαq*44 mice
heart failure ; cardiac aging ; Tgαq*44 mouse ; transcriptomics
There is an urgent need to understand the mechanisms underlying the cardiac aging and development of heart failure (HF) in order to develop new therapeutic strategies for cardiac pathophysiology. The aim of the study was to identify the mechanisms of cardiac aging in the course of HF development in Tgαq*44 mice and describe the relationship between cardiac aging process and development of HF. These mechanisms were investigated at the functional, morphological, hormonal and transcriptomic level. The early activated process of cardiac aging in the hearts of Tgαq*44 mice was characterized by impaired diastolic function, which seemed to be induced by increased fibrosis and remodeling of the extracellular matrix and functional disturbances in coronary microcirculation. HF induced more pronounced changes in the cardiac transcriptome of Tgαq*44 mice than the aging process in the cardiac transcriptome of FVB control mice. Aging process was accelerated by HF in the hearts of Tgαq*44 mice from early until the end-stage HF as evidenced by changes in genes expression and induced biological processes related to aging process. In the early stage of HF in Tgαq*44 mice, there are pathophysiological elements of HF that may be associated with premature activation of the aging process in the hearts of Tgαq*44 mice, as they are also present in the aged FVB mice.