HMGB1 and COX2 are regulated during organ damage following obesity-induced hypertension in a metabolic syndrome mouse model.

Obesity-associated hypertension induces organ damage and it is important to identify the protein responsible for initiating organ damage involves a complex pathological mechanism which most likely consists of multiple players that alters the normal physiology. The present study focuses mainly on identifying the role of HMGB1 in cardiac and renal tissue damage following obesity-induced hypertension. Following high-fat diet and leptin injection, mice developed obesity-induced initial hypertension and critical hypertension after 4 and 9 months, respectively. Histology, Immunohistochemistry, Western blotting, and siRNA were used for analysis. Histopathological analysis showed that the compact nature of cardiac and renal tissues began to loosen at the initial stages of organ damage. At the advanced stages of organ damage, cardiac tissue hardened, and renal tissue exhibited fibrosis development. Immunohistochemistry and western blotting studies revealed that HMGB1 expression was elevated in cardiac and renal tissues following initial hypertension-induced organ damage, but its expression was downregulated at critical stages of organ damage. The inflammatory marker COX2 exhibited a gradually upregulated expression pattern as organ damage progressed. Silencing of HMGB1 expression after the development of initial organ damage significantly reduced COX2 expression, but its suppression at the advanced stage of organ damage was associated with increased COX2 expression. Our study shows that HMGB1 plays a key role in initiating organ damage following obesity-induced hypertension, and that once damage reaches a certain level, HMGB1 expression is downregulated.