T-lymphocytes mediate left ventricular fibrillar collagen cross-linking and diastolic dysfunction in mice.

Aberrant concentrations of cardiac extracellular matrix (ECM) fibrillar collagen cross-linking have been proposed to be an underlying cause of cardiac diastolic dysfunction however the role of the adaptive immune system in this process has yet to be investigated. Fibrillar collagen cross-linking is a product of the enzymatic activities of lysyl oxidase (LOX and LOXL-3) released by the cardiac fibroblast and possibly cardiac myocytes. Our hypothesis is that stimulation of the TH1 lymphocytes activates lysyl oxidase mediated ECM cross-linking and thereby alters left ventricular function.

T lymphocyte regulation of lysyl oxidase in diet-induced cardiac fibrosis.

Left ventricular diastolic dysfunction is an important predictor of prognosis and mortality of heart failure. Increased left ventricular stiffness can be associated with excessive myocardial fibrosis and increased cross-linked collagen by the enzyme lysyl oxidase (LOX). These cardiac extracellular matrix (ECM) remodeling processes are affected by T-lymphocyte function and phenotype.

Myocardial lysyl oxidase regulation of cardiac remodeling in a murine model of diet-induced metabolic syndrome.

Metabolic syndrome (MetS) represents an increased risk of cardiovascular disease. Although its individual components adversely affect cardiac structure and function, the extent to which multiple components of MetS affect the cardiac extracellular matrix (ECM) has not been well characterized. Lysyl oxidase (LOX) is one of the cardiac ECM-modifying enzymes that catalyze the formation of collagen cross-linking.

IL-18 induction of osteopontin mediates cardiac fibrosis and diastolic dysfunction in mice.

Osteopontin (OPN), a key component of the extracellular matrix, is associated with the fibrotic process during tissue remodeling. OPN and the cytokine interleukin (IL)-18 have been shown to be overexpressed in an array of human cardiac pathologies. In the present study, we determined the role of IL-18 in the regulation of cardiac OPN expression and the subsequent interstitial fibrosis and diastolic dysfunction.

Comparative effects of dehydroepiandrosterone sulfate on ventricular diastolic function with young and aged female mice.

The adrenal steroid hormone dehydroepiandrosterone (DHEA) and its sulfated derivative [DHEA(S)] have been extensively studied for their potential anti-aging effects. Associated with aging, DHEA levels decline in humans, whereas other adrenal hormones remain unchanged, suggesting that DHEA may be important in the aging process. However, the effect of DHEA(S) supplementation on cardiac function in the aged has not been investigated.

Nutritional regulation of immunosenescence for heart health.

Immunosenescence via increased inflammatory cytokines may play key regulatory roles in facilitating cardiac infections and heart failure. Based upon recent evidence, we hypothesize that cytokine polarization due to aging directly dysregulates fibroblasts, leading to altered cardiac structure and dysfunction. Some dietary fatty acids should ameliorate heightened inflammatory cytokines thereby retarding cardiac pathology, loss of structural collagen and premature death from heart failure.