Innate Immune Cells in Pressure Overload-Induced Cardiac Hypertrophy and Remodeling

Abstract

Pressure overload and heart failure are among the leading causes of cardiovascular morbidity and mortality. Accumulating evidence suggests that inflammatory cell activation and release of inflammatory mediators are of vital importance during the pathogenesis of these cardiac diseases. Yet, the roles of innate immune cells and subsequent inflammatory events in these processes remain poorly understood. Here, we outline the possible underlying mechanisms of innate immune cell participation, including mast cells, macrophages, monocytes, neutrophils, dendritic cells, eosinophils, and natural killer T cells in these pathological processes. Although these cells accumulate in the atrium or ventricles at different time points after pressure overload, their cardioprotective or cardiodestructive activities differ from each other. Among them, mast cells, neutrophils, and dendritic cells exert detrimental function in experimental models, whereas eosinophils and natural killer T cells display cardioprotective activities. Depending on their subsets, macrophages and monocytes may exacerbate cardiodysfunction or negatively regulate cardiac hypertrophy and remodeling. Pressure overload stimulates the secretion of cytokines, chemokines, and growth factors from innate immune cells and even resident cardiomyocytes that together assist innate immune cell infiltration into injured heart. These infiltrates are involved in pro-hypertrophic events and cardiac fibroblast activation. Immune regulation of cardiac innate immune cells becomes a promising therapeutic approach in experimental cardiac disease treatment, highlighting the significance of their clinical evaluation in humans.

Integrated Bioinformatics Identifies FREM1 as a Diagnostic Gene Signature for Heart Failure

“…Activation of CD4+ T cells inhibits ventricular remodeling, and inhibition of mast cell degranulation reduces cardiac dysfunction. Liu et al's research found that neutrophils exert harmful functions in experimental models of heart failure caused by pressure overload [ 31 ]. This finding is consistent with the basic mechanism of action of neutrophils, which can participate in the occurrence and development of various cardiovascular diseases by releasing degranulation and recruiting microvesicles.…”

Common and Distinctive Intercellular Communication Patterns in Human Obstructive and Nonobstructive Hypertrophic Cardiomyopathy

“…Another striking feature is the skewed distribution of the altered signaling response, which is most pronounced in fibroblasts, dendritic cells, leukocytes and smooth muscle cells, suggesting that they play a larger role in nonobstructive HCM than in obstructive HCM. These findings raise the interesting possibility that fibroblasts, dendritic cells, leukocytes and smooth muscle cells play key roles in the pathogenesis of nonobstructive HCM, perhaps through regulation of the extracellular matrix, immune system activation and microvascular occlusion, all of which are known to occur in pathological hypertrophy and HCM [1,26,37].…”

Single Nucleus RNA-sequencing Reveals Altered Intercellular Communication and Dendritic Cell Activation in Nonobstructive Hypertrophic Cardiomyopathy

“…A notable difference between obstructive and nonobstructive HCM in our current study, however, involves the unexpected increases in communication between fibroblasts, smooth muscle cells and pericytes with dendritic cells and between smooth muscle cells and leukocytes in the nonobstructive HCM condition relative to the control condition. Immune cells have been demonstrated to play important roles in development of cardiac hypertrophy and fibrosis in a pressure overload model of rodent hypertrophy (reviewed in [ 35 ]). Dendritic cells function as antigen presenting cells that activate T cell responses and depletion of these cells reduces cardiomyocyte hypertrophy, cardiac fibrosis, LV remodeling and inflammatory cell infiltration after pressure overload [ 36 ].…”