Mast cells in human and experimental cardiometabolic diseases

Abstract

Mast cells, like many other types of inflammatory cell, perform pleiotropic roles in cardiometabolic diseases such as atherosclerosis, abdominal aortic aneurysms, obesity, and diabetes mellitus, as well as complications associated with these diseases. Low numbers of mast cells are present in the heart, aorta, and adipose tissue of healthy humans, but patients with cardiometabolic diseases and animals with experimentally-induced cardiometabolic pathologies have high numbers of mast cells with increased activity in the affected tissues. Mediators released by the activated mast cells, such as chemokines, cytokines, growth factors, heparin, histamine, and proteases, not only function as biomarkers of cardiometabolic diseases, but might also directly contribute to the pathogenesis of such diseases. Mast-cell mediators impede the functions of vascular cells, the integrity of the extracellular matrix, and the activity of other inflammatory cells, thereby contributing to the pathobiology of the conditions at multiple levels. In mouse models, mast-cell activation aggravates the progression of various cardiometabolic pathologies, whereas a genetic deficiency or pharmacological stabilization of mast cells, or depletion or inhibition of specific mast-cell mediators, tends to delay the progression of such conditions. Pharmacological inhibition of mast-cell activation or their targeted effector functions offers potential novel therapeutic strategies for patients with cardiometabolic disorders.

Current Knowledge and Perspectives on Histamine H1and H2Receptor Pharmacology: Functional Selectivity, Receptor Crosstalk, and Repositioning of Classic Histaminergic Ligands

“…In addition to H 2 R's classic regulation of gastric acid secretion, H 2 R signaling has also been implicated in the development of cardiovascular disease. High concentrations of histamine are found in cardiac tissues and the positive inotropic effects mediated by H 2 R stimulation may be important in the pathophysiology of cardiovascular disease (Eckel et al, 1982;Kirch et al, 1992;Hattori, 1999;Shi et al, 2015). In fact, the blocking of histamine release or H 2 R antagonism prevented heart failure in rabbits with doxorubicin-induced cardiomyopathy and dogs with sustained atrial tachycardia (Takahama et al, 2010).…”

Lymphatic System in Cardiovascular Medicine

“…Continuous recruitment of monocytes into plaques drives the progression of this chronic inflammatory condition, and athereosclerotic inflammation is sustained at least in part by the deposition of cholesterol crystals and undesirable immunity against cholesterol-associated apolipoproteins. [174][175][176] Although the link between cholesterol and inflammation that drives disease progression is not completely understood, it is established that removal of cholesterol from the arterial wall comprises a step toward regression of atherosclerosis. 177 The multistep process of cholesterol mobilization from extravascular tissues to biliary and nonbiliary excretion is termed reverse cholesterol transport (RCT).…”

Differential Regulation of Mas-Related G Protein-Coupled Receptor X2-Mediated Mast Cell Degranulation by Antimicrobial Host Defense Peptides and Porphyromonas gingivalis Lipopolysaccharide

“…In addition to chronic inflammation at the initial site of infection, P. gingivalis also contributes to systemic inflammation, such as atherosclerosis, which is dependent on the presence of mast cells (70)(71)(72)(73). The differential effects of PgLPS 1690 and PgLPS 1435/1449 on HDP/MRGPRX2-mediated mast cell degranulation may therefore modulate chronic inflammatory reactions at distal sites.…”