Effect of pathophysiological stressors on the tissue expression of parathyroid hormone-related protein (PTHrP)

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Myocardial infarction and sepsis are significant global health challenges. Myocardial ischemia results from blockages in coronary arteries, reducing blood flow and oxygen to the heart. Sepsis is a systemic immune response primarily triggered by bacterial infection. This study investigates the impact of high-fat diets and aging on the PTHrP system during ischemia/reperfusion, aiming to clarify the obesity paradox and the effects of hypothermia on vital organs, particularly the heart under endotoxemia. Findings indicate that PTHrP expression is age-dependent, with older mice showing higher levels than adults. A high-fat diet influenced PTHrP expression and its receptor, along with downstream molecules ADRP and PPARγ. Ischemia/reperfusion increased PTHrP and ADRP mRNA in the lungs, while having no significant effect on PTH-1R and PPARγ. LPS induced the PTHrP system in the lung and liver, but temperature changes did not significantly affect this. In contrast, the left ventricle exhibited downregulation of PTHrP and PTH-1R mRNA. In vitro and in vivo experiments demonstrated that hypothermia enhances PTHrP expression in the heart. Hypothermia also improved cardiac contractility and cell function under septic conditions. The study hypothesizes that a high-fat diet may enhance PTHrP expression in the lung during ischemia/reperfusion, potentially stabilizing pulmonary remodeling and contributing to the obesity paradox, while hypothermi