Reciprocal Multifaceted Interaction Between HDL (High-Density Lipoprotein) and Myocardial Infarction

Spósito, Andrei C.; Lima-Júnior, José Carlos de; Moura, Filipe A.; Barreto, Joaquim; Bonilha, Isabella; Santana, Michele Fraga de; Virginio, Vitor W.M.; Sun, Lili; Carvalho, Luiz Sérgio F.; Soares, Ana Flávia; Nadruz, Wilson; Feinstein, Steve B.; Nofer, Jerzy–Roch; Zanotti, Ilaria; Kontush, Anatol; Remaley, Alan T.

doi:10.1161/atvbaha.119.312880

Cited by 33 publications

(31 citation statements)

References 147 publications

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“…The ability of cardiac tissue to recover after MI is affected by numerous complex cellular and molecular pathways (7). Despite decades of therapeutic advances, MI remains a leading cause of death (8). In such a context, it is urgent to search for effective molecular pathways to provide insight into the prevention and management of MI.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: Silencing CircHIPK3 Sponges miR-93-5p to Inhibit the Activation of Rac1/PI3K/AKT Pathway and Improves Myocardial Infarction-Induced Cardiac Dysfunction

Yang

et al. 2021

Front. Cardiovasc. Med.

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The ceRNA network involving circular RNAs (circRNAs) is essential in the cardiovascular system. We investigated the underlying ceRNA network involving circHIPK3 in myocardial infarction (MI). After an MI model was established, cardiac function was verified, and myocardial tissue damage in mice with MI was evaluated. A hypoxia model of cardiomyocytes was used to simulate MI in vivo, and the expression of and targeting relationships among circHIPK3, miR-93-5p, and Rac1 were verified. The apoptosis of cardiomyocyte was identified. Gain- and loss-of-functions were performed to verify the ceRNA mechanism. The MI-modeled mice showed cardiac dysfunction and enlarged infarct size. CircHIPK3 was highly expressed in mouse and cell models of MI. Silencing circHIPK3 reduced infarct size, myocardial collagen deposition, and myocardial apoptosis rate and improved cardiac function. CircHIPK3 sponged miR-93-5p, and miR-93-5p targeted Rac1. Overexpression of miR-93-5p inhibited MI-induced cardiomyocyte injury and eliminated the harmful effect of circHIPK3. CircHIPK3 acted as ceRNA to absorb miR-93-5p, thus promoting the activation of the Rac1/PI3K/AKT pathway. We highlighted that silencing circHIPK3 can upregulate miR-93-5p and then inhibit the activation of Rac1/PI3K/Akt pathway, which can improve MI-induced cardiac dysfunction.

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Section: Introductionmentioning

confidence: 99%

RETRACTED: Silencing CircHIPK3 Sponges miR-93-5p to Inhibit the Activation of Rac1/PI3K/AKT Pathway and Improves Myocardial Infarction-Induced Cardiac Dysfunction

Yang

et al. 2021

Front. Cardiovasc. Med.

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“…Our finding that hepatic SR-BI protein levels are increased in HDL- treated SHR presumably suggests enhanced HDL clearance and supports the maintenance of homeostatic steady state levels of HDL cholesterol. Nonetheless, changes in HDL composition and/or function in response to increased SR-BI expression cannot be excluded ( 60 , 61 ).…”

Section: Discussionmentioning

confidence: 99%

High Density Lipoprotein Reduces Blood Pressure and Protects Spontaneously Hypertensive Rats Against Myocardial Ischemia-Reperfusion Injury in an SR-BI Dependent Manner

Al-Jarallah

Babiker

2022

Front. Cardiovasc. Med.

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BackgroundHypertension is a key risk factor in the development of cardiovascular diseases. Elevation in blood pressure alters high density lipoprotein (HDL) function and composition. The exact role of HDL in cardiovascular complications observed in hypertension is however not clearly understood. HDL protected against myocardial ischemia/reperfusion (I/R) injury in normotensive rats. Nonetheless, it's not clear if restoration of HDL function and/or composition protects against myocardial I/R injury in spontaneously hypertensive rats (SHR).ObjectivesIn this study we tested the effect of HDL treatment on I/R injury in Wistar Kyoto rats (WKY) and SHR and investigated the possible underlying mechanism(s).MethodsHDL (900 ng/kg/min) or vehicle were continuously administered to 11-week old WKY and SHR for 1 week (chronic treatment). Blood pressure was measured before and after treatment. Hearts were subjected to I/R injury using a modified Langendorff system. Another set of rats were treated with HDL administered at reperfusion (acute treatment) in the presence or absence of scavenger receptor class B type-I (SR-BI) blocking antibody. Cardiac hemodynamics were computed and cardiac enzyme release and infarct size were measured. Total cholesterol (TC) and HDL-cholesterol (HDL-C) were enzymatically assayed. Markers of autophagy and inflammation were detected by immunoblotting and ELISA, respectively.ResultsHDL treatment did not increase TC or HDL-C levels in SHR or WKY, yet it significantly (P < 0.01) reduced systolic and diastolic blood pressure in SHR. Chronic and acute HDL treatment significantly (P < 0.05) protected WKY and SHR against myocardial I/R injury. Chronic HDL treatment was significantly (P < 0.05) more protective in SHR whereas acute HDL treatment induced significantly (P < 0.05) greater protection in WKY. The extent of HDL induced protection was proportional to the expression levels of cardiac SR-BI and blockage of SR-BI completely abolished HDL mediated protection in SHR. Chronic HDL treatment significantly (P < 0.05) reduced markers of autophagy and inflammation in hypertensive rats.ConclusionsWe demonstrate a novel anti-hypertensive and a cardioprotective effect of HDL against myocardial I/R injury in SHR, the magnitude of which is directly related to the expression levels of cardiac SR-BI. Mechanistically, chronic HDL treatment protected SHR hearts by reducing autophagy and inflammation.

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“…Since CSL-112 appears to enhance cholesterol efflux similarly in healthy individuals and stable atherosclerotic patients [79], CSL-112 is being evaluated in the AEGIS II study, a randomised placebo-controlled study evaluating a single infusion of 6 g of apo AI in 17,000 patients with myocardial infarction (MI). It has been noted that this dose may be relatively small compared with the total plasma apo AI pool and it also possible that a late enrolment of patients (7 days after MI) may not be suitable to mitigate the injury of ischemia/ reperfusion [11].…”

Section: Hdl Therapythe Coronary Atheroma Target (Figure 1)mentioning

confidence: 99%

“…S1P rapidly reaches high plasma concentrations being bound to albumin or HDL. This bioactive PL can influence the quality and quantity of HDL dependent function, particularly with the binding partner apolipoprotein M; ApoM deficient mice do not carry S1P and show a functional deficiency of HDL [11]. Cellular protection may be exerted also by way of opening of the mitochondrial channels, exerted by S1P, apo AI, clusterin and miRNA [12,13].…”

Section: Introductionmentioning

confidence: 99%

HDL therapy today: from atherosclerosis, to stent compatibility to heart failure

et al. 2019

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Epidemiologically, high-density lipoprotein (HDL) cholesterol levels have been inversely associated to cardiovascular (CV) events, although a Mendelian Randomisation Study had failed to establish a clear causal role. Numerous atheroprotective mechanisms have been attributed to HDL, the main being the ability to promote cholesterol efflux from arterial walls; anti-inflammatory effects related to HDL ligands such as S1P (sphingosine-1-phosphate), resolvins and others have been recently identified. Experimental studies and early clinical investigations have indicated the potential of HDL to slow progression or induce regression of atherosclerosis. More recently, the availability of different HDL formulations, with different phospholipid moieties, has allowed to test other indications for HDL therapy. Positive reports have come from studies on coronary stent biocompatibility, where the use of HDL from different sources reduced arterial cell proliferation and thrombogenicity. The observation that low HDL-C levels may be associated with an enhanced risk of heart failure (HF) has also suggested that HDL therapy may be applied to this condition. HDL infusions or apoA-I gene transfer were able to reverse heart abnormalities, reduce diastolic resistance and improve cardiac metabolism. HDL therapy may be effective not only in atherosclerosis, but also in other conditions, of relevant impact on human health. KEY MESSAGES High-density lipoproteins have as a major activity that of removing excess cholesterol from tissues (particularly arteries). Knowledge on the activity of high-density lipoproteins on health have however significantly widened. HDL-therapy may help to improve stent biocompatibility and to reduce peripheral arterial resistance in heart failure.

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Reciprocal Multifaceted Interaction Between HDL (High-Density Lipoprotein) and Myocardial Infarction

Cited by 33 publications

References 147 publications

RETRACTED: Silencing CircHIPK3 Sponges miR-93-5p to Inhibit the Activation of Rac1/PI3K/AKT Pathway and Improves Myocardial Infarction-Induced Cardiac Dysfunction

RETRACTED: Silencing CircHIPK3 Sponges miR-93-5p to Inhibit the Activation of Rac1/PI3K/AKT Pathway and Improves Myocardial Infarction-Induced Cardiac Dysfunction

High Density Lipoprotein Reduces Blood Pressure and Protects Spontaneously Hypertensive Rats Against Myocardial Ischemia-Reperfusion Injury in an SR-BI Dependent Manner

HDL therapy today: from atherosclerosis, to stent compatibility to heart failure

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