Lp-PLA2 inhibition prevents Ang II-induced cardiac inflammation and fibrosis by blocking macrophage NLRP3 inflammasome activation

Lv, Silin; Zeng, Zheng-pei; Gan, Wenxia; Wang, Weiqi; Li, Tiegang; Hou, Yufang; Zheng, Yan; Zhang, Rixin; Yang, Min

doi:10.1038/s41401-021-00703-7

Cited by 47 publications

(33 citation statements)

References 62 publications

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“…Ang II plays a great role in cardiac remodeling in hypertension, the process as a result of cardiomyocyte hypertrophy, inflammation, and fibrosis, inducing reduction of compliance and enhancing the heart failure risk [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

“…These phenomena have revealed that the development and progression of cardiac diseases are associated with high expression and production of a variety of proinflammatory mediators including TNF- α , IL-1 β , IL-6, IL-8, VCAM-1, and PECAM [ 21 – 23 ]. Because inflammation is implicated and plays a considerable role in the pathogenesis of a wide spectrum of cardiovascular diseases induced by Ang II, the relevance between inflammation and Ang II has aroused more and more attention [ 21 ]. In the present experiments, we detected an increase in serum Ang II levels induced by CIH, and subsequently the levels of proinflammatory factors (TNF- α , IL-1 β , IL-6, and IL-8) were memorably ascended.…”

Section: Discussionmentioning

confidence: 99%

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Silencing MR-1 Protects against Myocardial Injury Induced by Chronic Intermittent Hypoxia by Targeting Nrf2 through Antioxidant Stress and Anti-Inflammation Pathways

Wang

Zhang

et al. 2022

Journal of Healthcare Engineering

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Background. Patients with obstructive sleep apnea hypopnea syndrome (OSAHS) often have cardiac insufficiency mainly due to hypoxia/reperfusion injury caused by chronic intermittent hypoxia (CIH). Inflammation and oxidative stress are involved in the cardiovascular events of OSAHS patients. Studies have found that myofibrillation regulator-1 (MR-1) participates in the pathological process of OSAHS-induced myocardial injury, but the specific mechanism is still unclear. Methods. We used a CIH-induced rat model to simulate the process of OSAHS disease. Indices of myocardial injury, inflammation, and oxidative stress were detected using quantitative PCR and enzyme-linked immunosorbent assay (ELISA). After administration of adenoassociated viral vector (AAV) encoding silencing RNA against MR-1, we examined expression of the classic antioxidant stress pathway protein NF-E2-related factor 2 (Nrf2) using western blotting. Results. We found that levels of serum inflammatory factors tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8 were increased, and we further observed disturbance of the oxidative stress system, in which the content of reactive oxygen species (ROS), superoxide dismutase (SOD), reduced glutathione (GSH), and malondialdehyde (MDA) was enhanced in CIH-induced rats. Subsequently, we detected that expression of Nrf2 and heme oxygenase-1 (HO-1) was slightly increased, while the expression of Kelch-like ECH-associated protein 1 (Keap-1) was significantly increased in the CIH model. Interestingly, after administration of silencing MR-1 AAV, the elevated levels of inflammatory factors were reduced, and the disordered oxidative stress system was corrected. Additionally, the expression of Nrf2 and HO-1 was distinctly increased, but the high expression of Keap-1 was decreased. Conclusions. Our research results demonstrate that silencing MR-1 rescued the myocardium the injury from inflammatory and oxidative stress in CIH-induced rats by administration of the Nrf2 signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Silencing MR-1 Protects against Myocardial Injury Induced by Chronic Intermittent Hypoxia by Targeting Nrf2 through Antioxidant Stress and Anti-Inflammation Pathways

Wang

Zhang

et al. 2022

Journal of Healthcare Engineering

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“…A study by Lv et al found that the expression of NLRP3 and IL-1β was significantly elevated in cardiac tissues in mouse model of angiotensin 2 (Ang II) infusion-induced hypertension, with a facilitative effect on the conversion of fibroblasts to myofibroblasts. 56 Triptolide, an immunomodulator, exerts dose-dependent anti-cardiac fibrosis effects by inhibiting both the activation of the inflammasome and the release of IL-1β in AngII-stimulated cardiac fibrosis. 57 The rupture of unstable coronary atherosclerotic plaques is the main cause of acute myocardial infarction, and the ischemic necrotic myocardium can release large amounts of ATP and oxidative stress products (reactive oxygen species) to activate the NLRP3 inflammasome.…”

Section: The Nlrp3 Inflammasome In the Development Of Cardiac Fibrosismentioning

confidence: 99%

The NLRP3 Inflammasome as a Novel Therapeutic Target for Cardiac Fibrosis

Fan¹,

Ren²,

Adhikari³

et al. 2022

JIR

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Cardiac fibrosis often has adverse cardiovascular effects, including heart failure, sudden death, and malignant arrhythmias. However, there is no targeted therapy for cardiac fibrosis. Inflammation is known to play a crucial role in the disorder, and the NLR pyrin domain-containing-3 (NLRP3) inflammasome is closely associated with innate immunity. Therefore, further understanding the pathophysiological role of the inflammasome in cardiac fibrosis may provide novel strategies for the prevention and treatment of the disorder. The aim of this review was to summarize the present knowledge of NLRP3 inflammasome-related mechanisms underlying cardiac fibrosis and to suggest potential targeted therapy that could be used to treat the condition.

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“…Also, down-regulation of PLA2G7 has been shown to delay cardiac aging after caloric restriction [72]. LPA2 inhibition has been attributed to anti-inflammatory and anti-fibrotic benefits seen in a model of hypertensive cardiac disease [73]. By down-regulating PLA2G7 and, consequently, reducing LPA2 expression miR-1183 might display a protective role against inflammatory cardiac remodeling, cardiac aging, and fibrosis.…”

Section: Downstream Targets Of Mir-1183 and Cardiac Functional Effectsmentioning

confidence: 99%

miR-1183 Is a Key Marker of Remodeling upon Stretch and Tachycardia in Human Myocardium

Djalinac

Kolesnik

Maechler

et al. 2022

IJMS

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Many cardiac insults causing atrial remodeling are linked to either stretch or tachycardia, but a comparative characterization of their effects on early remodeling events in human myocardium is lacking. Here, we applied isometric stretch or sustained tachycardia at 2.5 Hz in human atrial trabeculae for 6 h followed by microarray gene expression profiling. Among largely independent expression patterns, we found a small common fraction with the microRNA miR-1183 as the highest up-regulated transcript (up to 4-fold). Both, acute stretch and tachycardia induced down-regulation of the predicted miR-1183 target genes ADAM20 and PLA2G7. Furthermore, miR-1183 was also significantly up-regulated in chronically remodeled atrial samples from patients with persistent atrial fibrillation (3-fold up-regulation versus sinus rhythm samples), and in ventricular myocardium from dilative cardiomyopathy hearts (2-fold up-regulation) as compared to non-failing controls. In sum, although stretch and tachycardia show distinct transcriptomic signatures in human atrial myocardium, both cardiac insults consistently regulate the expression of miR-1183 and its downstream targets in acute and chronic remodeling. Thus, elevated expression of miR-1183 might serve as a tissue biomarker for atrial remodeling and might be of potential functional significance in cardiac disease.

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Lp-PLA2 inhibition prevents Ang II-induced cardiac inflammation and fibrosis by blocking macrophage NLRP3 inflammasome activation

Cited by 47 publications

References 62 publications

Silencing MR-1 Protects against Myocardial Injury Induced by Chronic Intermittent Hypoxia by Targeting Nrf2 through Antioxidant Stress and Anti-Inflammation Pathways

Silencing MR-1 Protects against Myocardial Injury Induced by Chronic Intermittent Hypoxia by Targeting Nrf2 through Antioxidant Stress and Anti-Inflammation Pathways

The NLRP3 Inflammasome as a Novel Therapeutic Target for Cardiac Fibrosis

miR-1183 Is a Key Marker of Remodeling upon Stretch and Tachycardia in Human Myocardium

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