Abstract
Cardiac remodeling occurs frequently in chronic kidney disease patients and affects quality of life and survival. Current treatment options are highly inadequate. As kidney function declines, numerous metabolic pathways are disturbed. Kidney and heart functions are highly connected by organ crosstalk. Among others, altered volume and pressure status, ischemia, accelerated atherosclerosis and arteriosclerosis, disturbed mineral metabolism, renal anemia, activation of the renin-angiotensin system, uremic toxins, oxidative stress and upregulation of cytokines stress the sensitive interplay between different cardiac cell types. The fatal consequences are left-ventricular hypertrophy, fibrosis and capillary rarefaction, which lead to systolic and/or diastolic left-ventricular failure. Furthermore, fibrosis triggers electric instability and sudden cardiac death. This review focuses on established and potential pathophysiological cardiorenal crosstalk mechanisms that drive uremia-induced senescence and disease progression, including potential known targets and animal models that might help us to better understand the disease and to identify novel therapeutics.
Highlights
Cardiac remodeling occurs frequently in chronic kidney disease patients and affects quality of life and survival
We have reported that Gli1 marks a specific perivascular cell type that drives cardiac fibrosis and vascular calcification [30,31]
The Chronic Renal Insufficiency Cohort Study (CRIC) study found that elevated plasma levels of high-sensitivity C-reactive protein and IL-6 were associated with left-ventricular hypertrophy (LVH)
Summary
Chronic kidney disease (CKD) affects an increasing number of patients worldwide and is associated with dramatically increased morbidity and mortality [1,2]. Other essential cell types include endothelial cells, fibroblasts, vascular smooth muscle cells and perivascular cells [6,7]. Each cardiomyocyte is in physical contact with at least one capillary, allowing mechanical and paracrine crosstalk between at least four key cell types, namely, cardiomyocytes, endothelial cells, vascular smooth muscle cells (VSMCs) and pericytes/fibroblasts [11]. Cardiomyocytes crosstalk with endothelial cells and fibroblasts by secreting various specific growth factors [7]. Various lines of evidence suggest that endothelial cells crosstalk with cardiomyocytes and are key players in angiogenesis and vasomotor tone control by secreting angiocrine factors such as nitric oxide or endothelin-1 [12]. The cardiac morphology and function can be affected by further external and internal stimuli
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