High-density lipoprotein protects cardiomyocytes against necrosis induced by oxygen and glucose deprivation through SR-B1, PI3K, and AKT1 and 2

Durham, Kristina; Chathely, Kevin M.; Trigatti, Bernardo L.

doi:10.1042/bcj20170703

Cited by 33 publications

(25 citation statements)

References 38 publications

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“…Not surprisingly, the absence of PDZK1 did not permit the athero-protective effects of HDL against apoptosis, highlighting the importance of PDZK1 in mediating HDL signalling in macrophages. Consistently, in another study by this group earlier this year [11], they showed that HDL signalling via SR-BI and Akt protected cardiomyocyte necrosis in response to oxygen and glucose deprivation in vitro.…”

supporting

confidence: 75%

Beyond cholesterol homeostasis: A novel role for PDZK1 in macrophage apoptosis and atherosclerosis

Karunakaran

2018

Atherosclerosis

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supporting

confidence: 75%

Beyond cholesterol homeostasis: A novel role for PDZK1 in macrophage apoptosis and atherosclerosis

Karunakaran

2018

Atherosclerosis

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“…While our analysis of HDL modification was limited to detection of protein cross‐linking, it is possible that some reactive aldehydes preferentially modify nonprotein components of HDL. Additionally, the majority of our studies was performed using primary peritoneal macrophages that were isolated from mice 4 days postinjection with 4% thioglycolate, a model system that has been routinely used for studies of lipoprotein metabolism . We chose thioglycolate‐elicited macrophages for our studies for several reasons.…”

Section: Discussionmentioning

confidence: 99%

Modification of HDL by reactive aldehydes alters select cardioprotective functions of HDL in macrophages

et al. 2019

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While increased levels of high‐density lipoprotein (HDL)‐cholesterol correlate with protection against cardiovascular disease, recent findings demonstrate that HDL function, rather than HDL‐cholesterol levels, may be a better indicator of cardiovascular risk. One mechanism by which HDL function can be compromised is through modification by reactive aldehydes such as acrolein (Acro), 4‐hydroxynonenal, and malondialdehyde (MDA). In this study, we tested the hypothesis that modification of HDL with reactive aldehydes would impair HDL’s athero‐protective functions in macrophages. Compared to native HDL, Acro‐ and MDA‐modified HDL have impaired abilities to promote migration of primary peritoneal macrophages isolated from C57BL6/J mice. Incubation of macrophages with MDA‐HDL also led to an increased ability to generate reactive oxygen species. Our studies revealed that the changes in HDL function following aldehyde modification are likely not through activation of canonical nuclear factor‐kappa B signaling pathways. Consistent with this finding, treatment of either noncholesterol‐loaded macrophages or foam cells with modified forms of HDL does not lead to significant changes in expression levels of inflammatory markers. Importantly, our data also demonstrate that changes in HDL function are dependent on the type of modification present on the HDL particle. Our findings suggest that modification of HDL with reactive aldehydes can impair some, but not all, of HDL’s athero‐protective functions in macrophages.

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“…Durham et al [ 19 ] demonstrated that HDLs protect cardiomyocytes against necrosis induced by oxygen and glucose deprivation via a mechanism involving scavenger receptor class B, type 1 (SR-BI). HDL treatment resulted in the phosphorylation of protein kinase B (Akt) in cardiomyocytes in SR-BI +/+ cardiomyocytes, but not in SR-BI −/− cardiomyocytes.…”

Section: Biological Mechanisms That May Contribute To the Beneficimentioning

confidence: 99%

High-Density Lipoprotein-Targeted Therapies for Heart Failure

Mishra

Geest

2020

Biomedicines

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The main and common constituents of high-density lipoproteins (HDLs) are apolipoprotein A-I, cholesterol, and phospholipids. Biochemical heterogeneity of HDL particles is based on the variable presence of one or more representatives of at least 180 proteins, 200 lipid species, and 20 micro RNAs. HDLs are circulating multimolecular platforms that perform divergent functions whereby the potential of HDL-targeted interventions for treatment of heart failure can be postulated based on its pleiotropic effects. Several murine studies have shown that HDLs exert effects on the myocardium, which are completely independent of any impact on coronary arteries. Overall, HDL-targeted therapies exert a direct positive lusitropic effect on the myocardium, inhibit the development of cardiac hypertrophy, suppress interstitial and perivascular myocardial fibrosis, increase capillary density in the myocardium, and prevent the occurrence of heart failure. In four distinct murine models, HDL-targeted interventions were shown to be a successful treatment for both pre-existing heart failure with reduced ejection fraction (HFrEF) and pre-existing heart failure with preserved ejection fraction (HFrEF). Until now, the effect of HDL-targeted interventions has not been evaluated in randomized clinical trials in heart failure patients. As HFpEF represents an important unmet therapeutic need, this is likely the preferred therapeutic domain for clinical translation.

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High-density lipoprotein protects cardiomyocytes against necrosis induced by oxygen and glucose deprivation through SR-B1, PI3K, and AKT1 and 2

Cited by 33 publications

References 38 publications

Beyond cholesterol homeostasis: A novel role for PDZK1 in macrophage apoptosis and atherosclerosis

Beyond cholesterol homeostasis: A novel role for PDZK1 in macrophage apoptosis and atherosclerosis

Modification of HDL by reactive aldehydes alters select cardioprotective functions of HDL in macrophages

High-Density Lipoprotein-Targeted Therapies for Heart Failure

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