Immune modulation with TH1 inducers significantly increased left ventricular stiffness, whereas TH2 inducers decreased stiffness and increased ventricular volumes (P<0.01).
Does selective induction of TH1 versus TH2 lymphocytes alter cardiac diastolic function and extracellular matrix composition in mice?
The TH1/TH2 lymphocyte phenotype differentially regulates cardiac diastolic function and extracellular matrix remodeling, suggesting immune modulation as a potential therapeutic target in heart failure.
valor p: p=<0.01
The induction of T helper (TH) lymphocytes by distinct TH ligands results in a differentiation to TH1/TH2 subsets based on their unique pattern of cytokine secretion and effector functions. We hypothesized that the relative proportion of TH1/TH2 directly relates to cardiac fibroblast (CF) function and thereby cardiac extracellular matrix (ECM) composition and cardiac diastolic function in the absence of injury or altered wall stress. We compared the effect of selective TH1 with TH2 inducers on cardiac gene expression, ECM composition, and diastolic function in C57BL/J mice. Twelve weeks after immune modulation, the left ventricular stiffness (beta) was significantly increased in the TH1 group and decreased in the TH2 group (P < 0.01). The TH2 group also demonstrated significantly increased end-diastolic and end-systolic volumes (P < 0.01). Cardiac gene expression patterns for pro-matrix metalloproteinase (MMP)-9 and -13 were increased by greater than fivefold in the TH2 group and significantly decreased in the TH1 group (P < 0.05). The total cardiac collagen and cross-linked collagen were significantly increased in the TH1 group and decreased in the TH2 group (P < 0.01). Coculturing lymphocytes harvested from the treated mice with naive primary CF demonstrated a direct control of the lymphocytes on CF pro-collagen, pro-MMP gene expression, and MMP activity. These results suggest that the TH phenotype differentially affects diastolic function through modulating CF pro-collagen and pro-MMP gene expression, MMP activity, and cardiac collagen cross-linking, resulting in altered ECM composition. Thus modulation of TH lymphocyte function could promote adaptive remodeling in heart failure and postmyocardial infarction.
Yu et al. (Wed,) conducted a other in Cardiac diastolic function and extracellular matrix composition. Selective TH1 and TH2 inducers vs. TH1 vs TH2 groups was evaluated on Left ventricular stiffness (beta) (p=<0.01). Immune modulation with TH1 inducers significantly increased left ventricular stiffness, whereas TH2 inducers decreased stiffness and increased ventricular volumes (P<0.01).