resolvin-d1 and Hypertension

Vascular structure and integrity are at the forefront of blood pressure regulation. However, there are many factors that affect the responses of the vessels. One of these is the inflammatory processes associated with high cholesterol and its modification. 15-lipoxygenase (15-LOX) is the critical enzyme in cholesterol oxidation, but this enzyme is also responsible for the synthesis of specialized proresoving lipid mediators (SPMs) called Lipoxin (Lxs) and Resolvin (Rvs). In this study, we determined serum LXA4, RvD1 and RvE1 levels in newly diagnosed hypertension (HT) and normotension (NT) cases. We evaluated how the presence of hypercholesterolemia (HC) in the follow-up changes the levels of these SPMs. We found that the three SPMs we measured decreased significantly in the presence of HC. In addition, we found a negative and significant correlation with systolic blood pressure and total cholesterol levels for the three SPMs. In conclusion, HT and HC are independent risk factors for cardiovascular death. However, the presence of HC may be an important factor for the development of HT. Increasing cholesterol levels may cause 15-LOX to shift towards LDL oxidation, thus leading to inflammation. This situation may negatively affect the vascular functions in the regulation of blood pressure. Serum LXA4, RvD1 and RvE1 measurements may provide clues that represent a shift of 15-LOX enzyme activity towards cholesterol.

Topics: Adult; Arachidonate 15-Lipoxygenase; Blood Pressure; Cholesterol; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids, Unsaturated; Female; Follow-Up Studies; Humans; Hypercholesterolemia; Hypertension; Lipoproteins, LDL; Lipoxins; Male; Middle Aged; Oxidation-Reduction; Risk Factors

Despite the broad pharmacological arsenal to treat hypertension, chronic patients may develop irreversible cardiac remodeling and fibrosis. Angiotensin II, the main peptide responsible for the Renin-Angiotensin-Aldosterone-System, has been closely linked to cardiac remodeling, hypertrophy, fibrosis, and hypertension, and some of these effects are induced by inflammatory mediators. Resolvin-D1 (RvD1) elicits potent anti-inflammatory and pro-resolving effects in various pathological models. In this study, we aimed to examine whether RvD1 ameliorates cardiac remodeling and hypertension triggered by angiotensin II.. Alzet® osmotic mini-pumps filled with angiotensin II (1.5 mg/kg/day) were implanted in male C57BL/6 J mice for 7 or 14 days. RvD1 (3 μg/kg/day, i.p) was administered one day after the surgery and during the complete infusion period. Blood pressure and myocardial functional parameters were assessed by echocardiography. At the end of the experimental procedure, blood and heart tissue were harvested, and plasma and histological parameters were studied. After 7 and 14 days, RvD1 reduced the increase of neutrophil and macrophage infiltration triggered by angiotensin II, and also reduced ICAM-1 and VCAM-1 expression levels. RvD1 also reduced cytokine plasma levels (IL-1β, TNF-α, IL-6, KC, MCP-1), cardiac hypertrophy, interstitial and perivascular fibrosis, and hypertension.. This study unveils novel cardioprotective effects of RvD1 in angiotensin II-induced hypertension and cardiac remodeling by attenuating inflammation and provides insights into a potential clinical application.

Topics: Angiotensin II; Animals; Cardiomegaly; Chemokine CCL2; Disease Models, Animal; Docosahexaenoic Acids; Gene Expression Regulation; Humans; Hypertension; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-1beta; Interleukin-6; Mice; Renin-Angiotensin System; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1; Ventricular Remodeling