Maresin 1 Modulates Cardiac and Renal Lipid Profiles in Hypertensive Rats
BACKGROUND: Chronic inflammation contributes significantly to hypertension and associated target organ damage, particularly in the heart and kidneys. Specialized pro-resolving mediators (SPMs), a class of bioactive lipids primarily derived from omega-3 fatty acids, play key roles in resolving inflammation and maintaining tissue homeostasis. Among them, Maresin 1 (MaR1) has been implicated in cardiovascular regulation and blood pressure control. We hypothesized that MaR1 may mitigate salt-induced hypertension and its related effects in Dahl salt-sensitive (SS) rats. This study evaluated the impact of MaR1 on blood pressure progression, cardiac function, fibrosis, lipid metabolism, gene expression, and circadian rhythms in SS rats fed a high-salt diet. METHODS: SS rats were fed a high-salt diet and treated with MaR1. Mean arterial pressure (MAP) and heart rate (HR) were continuously monitored. Echocardiography and histology were used to assess cardiac structure, contractility, and fibrosis. Lipidomic profiling quantified inflammation-resolving lipid mediators, and transcriptomic analysis identified organ-specific gene expression changes. RESULTS: MaR1 treatment did not significantly alter MAP, HR, or cardiac structure and function. Echocardiographic and histological evaluations showed no significant changes in cardiac remodeling, contractility, or collagen deposition in the heart or kidney. However, lipidomic profiling revealed shifts in inflammatory lipid mediators, suggesting immunomodulatory and metabolic effects of MaR1. Transcriptomic analysis demonstrated organ-specific gene expression changes, with upregulation of circadian and metabolic pathways in the heart and modulation of immune signaling in the kidney. Notably, MaR1 influenced circadian blood pressure rhythms, enhancing amplitude and shifting the acrophase, consistent with altered expression of circadian clock genes. CONCLUSIONS: Although MaR1 did not affect hypertension development directly, its modulation of lipid metabolism, inflammatory pathways, and circadian regulation suggests therapeutic potential. Future studies should explore extended treatment durations and combination strategies to fully evaluate its role in cardiovascular and renal disease management. Overall design: Male animals were used for the study.  At 8 weeks of age animals were implanted with a telemeter to measure chronic blood pressure. After a few days of recovery animals were switched to high salt (HS, 4% NaCl) diet for 3 weeks. Maresin 1 (MaR1, No. 1268720-28-0, Cayman Chemical Company) was administered subcutaneously via an implanted osmotic minipump (2ML4, ALZET Osmotic Pump) to deliver either the vehicle control or Maresin 1 at a dosage of up to 1.3 µg/kg/day continuously over 3 weeks HS challenge. After 3 weeks on HS, animals were anesthetized with isoflurane and kidneys were collected. Kidney cortex from one kidney and left ventricle of heart  were snap-frozen and used for transcriptomic analysis to compare gene expression in vehicle and MaR1-treated groups.