Low LXA4, RvD1 and RvE1 levels may be an indicator of the development of hypertension

Yücel, Habil; Özdemir, Alper Tunga

doi:10.1016/j.plefa.2021.102365

Cited by 7 publications

(8 citation statements)

References 25 publications

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“…33 Moreover, at the clinical level lower circulating levels of different SPMs such as RvDs have been found in patients with different cardiovascular diseases. 23,24,34,35 SPMs production depends on LOX enzymes expression and subcellular localization. For example, 5-LOX in the perinuclear region participates in the biosynthesis of proinflammatory LTB 4 and LTC 4 , 36 whereas 5-LOX in the cytoplasm is associated with SPM biosynthesis in vascular cells.…”

Section: Discussionmentioning

confidence: 99%

“…11,15,22 Moreover, decreased levels of some SPMs have been described in hypertensive patients compared with normotensive controls. 23 Resolvins such as RvD2 display direct protective actions in VSMC, modulating cell phenotype, 24,25 and contractility, 26 and stimulates nitric oxide (NO) and prostacyclin (PGI 2 ) production from endothelial cells, which limit excessive leukocyte infiltration and reduce pro-inflammatory cytokines. 27 More importantly, treatment with some SPMs such as RvD2 prevent atheroprogression, reduces neointima formation, and inhibits aortic abdominal aneurysm formation.…”

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confidence: 99%

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Resolvin D2 Attenuates Cardiovascular Damage in Angiotensin II-Induced Hypertension

et al. 2023

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BACKGROUND: Resolution of inflammation is orchestrated by specialized pro-resolving mediators (SPMs), and this would be impaired in some cardiovascular diseases. Among SPMs, resolvins (Rv) have beneficial effects in cardiovascular pathologies, but little is known about their effect on cardiovascular damage in hypertension. METHODS: Aorta, small mesenteric arteries, heart, and peritoneal macrophages were taken from C57BL/6J mice, infused or not with Angiotensin II (AngII 1.44 mg/kg/day, 14 days) in presence or absence of RvD2 (100 ng/mice, every second day) starting 1 day before or 7 days after AngII infusion. RESULTS: Enzymes and receptors involved in SPMs biosynthesis and signaling were increased in aorta or heart from AngII-infused mice. We also observed a differential regulation of SPMs in heart from these mice. Preventive treatment with RvD2 partially avoided AngII-induced hypertension and protected the heart and large and small vessels against functional and structural alterations induced by AngII. RvD2 increased the availability of vasoprotective factors, modified SPMs profile, decreased cardiovascular fibrosis, and increased the infiltration of pro-resolving macrophages. When administered in hypertensive animals with established cardiovascular damage, RvD2 partially improved cardiovascular function and structure, decreased fibrosis, reduced the infiltration of neutrophils, and shifted macrophage phenotype toward a pro-resolving phenotype. CONCLUSIONS: There is a disbalance between proinflammatory and resolution mediators in hypertension. RvD2 protects cardiovascular function and structure when administered before and after the development of hypertension by modulating vascular factors, fibrosis and inflammation. Activating resolution mechanisms by treatment with RvD2 may represent a novel therapeutic strategy for the treatment of hypertensive cardiovascular disease.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Resolvin D2 Attenuates Cardiovascular Damage in Angiotensin II-Induced Hypertension

et al. 2023

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“…* P < 0.05, * * P < 0.01, * * * P < 0.001, and * * * * P < 0.0001 vs. the PHT group. development of hypertension [63]. On the contrary, increased LXA4 in the plasma of preeclampsia women plays a central role in disease development [64].…”

Section: Discussionmentioning

confidence: 99%

“…A previous study showed that 12(R)-HETE acts as an agonist of the vasodilator in preconstricted mouse artery [ 61 ]. LXA4 has anti-inflammatory, vasodilatory, and antioxidant effects [ 62 ], and low LXA4 levels may be an indicator of the development of hypertension [ 63 ]. On the contrary, increased LXA4 in the plasma of preeclampsia women plays a central role in disease development [ 64 ].…”

Section: Discussionmentioning

confidence: 99%

Decompression Mechanism of Radish Seed in Prehypertension Rats through Integration of Transcriptomics and Metabolomics Methods

Jia

et al. 2023

Evidence-Based Complementary and Alternative Medicine

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Radish seed (RS), the dried ripe seed of Raphanus sativus L., is widely used in traditional Chinese medicine (TCM) to reduce blood pressure. However, the molecular and pharmacological mechanisms underlying its therapeutic effects are still unclear. In this study, we analyzed the effects of RS in a rat model of prehypertension and assessed the mechanistic basis by integrating transcriptomics and metabolomics. RS administration significantly reduced blood pressure in prehypertensive male Wistar rats, negatively regulated endothelin-1, increased nitric oxide levels, and reduced the exfoliation of endothelium cells. In vitro vascular ring experiments further confirmed the effects of RS on vascular endothelial cells. Furthermore, we identified 65 differentially expressed genes (DEGs; P a d j < 0.05 and fold change (FC) > 2) and 52 metabolites (VIP > 1, P < 0.05 and FC ≥ 2 or ≤0.5) in the RS intervention group using RNA-seq and UPLC-MS/MS, respectively. A network of the DEGs and the metabolites was constructed,q which indicated that RS regulates purine metabolism, linoleic acid metabolism, arachidonic acid metabolism, circadian rhythm, and phosphatidylinositol signaling pathway, and its target genes are Pik3c2a, Hspa8, Dnaja1, Arntl, Ugt1a1, Dbp, Rasd1, and Aldh1a3. Thus, the antihypertensive effects of RS can be attributed to its ability to improve vascular endothelial dysfunction by targeting multiple genes and pathways. Our findings provide new insights into the pathological mechanisms underlying prehypertension, along with novel targets for the prevention and treatment of hypertension.

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“…Inflammation has been demonstrated as a major component of hypertension and hypertension related organ damage, including peripheral vascular resistance and heart dysfunction. Although the direct relationship between MaR1 and hypertension has not been experimentally tested, by comparing the serum levels of lipoxin and Resolvins in hypertension and normotension patients, Yücel et al found that the lipoxin A4 (LXA4), RvD1 and Resolvin E1 (RvE1) levels were negatively correlated with systolic blood pressure and total cholesterol levels, implying that reduced SPMs may serve as indicators of the development of hypertension ( 44 ). Indeed, RvD1, which is also derived from DHA, had shown protective potential in angiotensin II induced hypertension and cardiac remodeling ( 45 ).…”

Section: Mar1 and Hypertensive Cardiovascular Diseasementioning

confidence: 99%

Protective Potential of Maresins in Cardiovascular Diseases

Liu

2022

Front. Cardiovasc. Med.

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Cardiovascular diseases are the leading causes of global mortality. Growing evidence suggests that unresolved inflammation contributes to the chronicity, progression and morbidity of many cardiovascular diseases, thus emphasizing the urgent need to illuminate the mechanisms controlling inflammation and its resolution, for the sake of new effective therapeutic options. Macrophage mediators in resolving inflammation (Maresins) are a family of specialized pro-resolving lipid mediators (SPMs) derived from the ω-3 fatty acid docosahexaenoic acid (DHA). Studies have indicated that Maresins play critical role in initiating the pro-resolving functions of phagocytes, decreasing the magnitude of the overall inflammatory response, and thereby protecting against inflammation-related disorders. In this review, we summarize the detailed actions and the therapeutic potential of Maresins, with a particular emphasis on Maresin-1 (MaR1), in cardiovascular diseases. We hope this review will lead to new avenues to Maresins-based therapies for inflammation-associated cardiovascular diseases.

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Low LXA4, RvD1 and RvE1 levels may be an indicator of the development of hypertension

Cited by 7 publications

References 25 publications

Resolvin D2 Attenuates Cardiovascular Damage in Angiotensin II-Induced Hypertension

Resolvin D2 Attenuates Cardiovascular Damage in Angiotensin II-Induced Hypertension

Decompression Mechanism of Radish Seed in Prehypertension Rats through Integration of Transcriptomics and Metabolomics Methods

Protective Potential of Maresins in Cardiovascular Diseases

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