HDL mimetic peptide CER-522 treatment regresses left ventricular diastolic dysfunction in cholesterol-fed rabbits

Merlet, Nolwenn; Busseuil, David; Mihalache-Avram, Téodora; Mecteau, Mélanie; Shi, Yanfen; Nachar, Walid; Brand, Geneviève; Brodeur, Mathieu R.; Charpentier, Daniel; Rhainds, David; Sy, Gavin; Lalwani, Narendra D.; Dasseux, Jean-Louis; Rhéaume, Éric; Tardif, Jean‐Claude

doi:10.1016/j.ijcard.2016.04.029

Cited by 11 publications

(12 citation statements)

References 38 publications

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“…Similarly, systolic s′ velocity increased during dobutamine infusion in dose-dependent manner and was strongly associated with dP/d t peak [39]. A direct association between HDL levels and LV longitudinal systolic and diastolic performance observed in our populations can be explained by studies showing that HDL increases insulin-independent glucose uptake in rat cardiomyocytes via an Akt signaling pathway [40] and that HDL mimetic peptide improves LV diastolic dysfunction in cholesterol-fed rabbits [41].…”

Section: Discussionmentioning

confidence: 90%

Cardiovascular organ damage in type 2 diabetes mellitus: the role of lipids and inflammation

Kozàkovà

Morizzo

Gonçalves

et al. 2019

Cardiovasc Diabetol

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Background The relationship between dyslipidemia, inflammation and CV organ damage in type 2 diabetes mellitus (T2DM) is complex. Insulin resistance and inflammatory cytokines interleukins (ILs) increase plasma triglycerides (TG). ILs also up-regulate expression of matrix-metalloproteinases (MMPs) that, together with TG, decrease high density lipoprotein cholesterol (HDL) levels. High TG, low HDL, increased ILs and MMPs trigger structural and functional changes in different parts of cardiovascular (CV) system. To understand better the role of lipids and inflammation in CV organ damage, the present study investigated the inter-relationships between lipids, ILs and MMPs, as well as the associations of lipids, ILs and MMPs with various CV measures, both in diabetic and non-diabetic population (nonT2DM). Methods In T2DM patients (N = 191) and nonT2DM subjects (N = 94) were assessed carotid intima-media thickness (cIMT) and inter-adventitial diameter (IADiam), carotid wave speed (ccaWS), carotid-femoral pulse wave velocity (cfPWV), left ventricular (LV) mass, LV systolic (s′) and early diastolic (e′) longitudinal velocities of mitral annulus, together with glycemic control, lipid profile, IL-6, IL-18 and MMP-12. Results T2DM patients, as compared to nonT2DM subjects, had significantly higher plasma levels of IL-6, IL-18, MMP-12 and lower HDL ( P < 0.05–0.0001). They had also higher cIMT, IADiam, ccaWS, cfPWV and LV mass, and lower e′ velocity ( P < 0.005–0.0001). Both in T2DM patients and nonT2DM subjects, MMP-12 increased with IL-6 (r = 0.43 and 0.39; P < 0.0001) and IL-18 (r = 0.32 and 0.42; P < 0.0001), and HDL decreased with MMP-12 (r = − 0.29 and − 0.42; P < 0.0001). In both populations, MMP-12 was directly associated with IADiam, ccaWS, cfPWV and LV mass (r = 0.42, 0.32, 0.26 and 0.29; P < 0.0001 in T2DM patients, and r = 0.39, 0.28, 0.32 and 0.27; P < 0.01–0.0001 in nonT2DM subjects). In multivariate analysis, MMP-12 remained independently related to IADiam, ccaWS, cfPWV and LV mass in T2DM patients, and to IADiam only in nonT2DM subjects. Conclusions This cross-sectional study demonstrated a direct association between ILs and MMP-12, as well as an inverse association between MMP-12 and HDL, both in T2DM patients and in nonT2DM subjects. In T2DM patients, who had higher levels of ILs and MMP-12, the latter was independently related to several structural and functional markers of preclinical CV organ damage. Electronic supplementary material The online version of this article (10.1186/s12933-019-0865-6) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 90%

Cardiovascular organ damage in type 2 diabetes mellitus: the role of lipids and inflammation

Kozàkovà

Morizzo

Gonçalves

et al. 2019

Cardiovasc Diabetol

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“…However, there were no significant differences in the variables of systolic function or in the dynamic measurements of either ventricle in the HC group. Therefore, it is likely that these data support some initial degree of altered ventricular relaxation, which may be due to initial states of systemic metabolic and inflammatory instability, such as hypercholesterolemia [ 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

Quercetin Prevents Diastolic Dysfunction Induced by a High‐Cholesterol Diet: Role of Oxidative Stress and Bioenergetics in Hyperglycemic Rats

Castillo

Herrera

Gonzaléz‐Candia

et al. 2018

Oxidative Medicine and Cellular Longevity

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Alterations in cardiac energy metabolism play a key role in the pathogenesis of diabetic cardiomyopathy. Hypercholesterolemia associated with bioenergetic impairment and oxidative stress has not been well characterized in the cardiac function under glycemic control deficiency conditions. This work aimed to determine the cardioprotective effects of quercetin (QUE) against the damage induced by a high-cholesterol (HC) diet in hyperglycemic rats, addressing intracellular antioxidant mechanisms and bioenergetics. Quercetin reduced HC-induced alterations in the lipid profile and glycemia in rats. In addition, QUE attenuated cardiac diastolic dysfunction (increased E:A ratio), prevented cardiac cholesterol accumulation, and reduced the increase in HC-induced myocyte density. Moreover, QUE reduced HC-induced oxidative stress by preventing the decrease in GSH/GSSG ratio, Nrf2 nuclear translocation, HO-1 expression, and antioxidant enzymatic activity. Quercetin also counteracted HC-induced bioenergetic impairment, preventing a reduction in ATP levels and alterations in PGC-1α, UCP2, and PPARγ expression. In conclusion, the mechanisms that support the cardioprotective effect of QUE in rats with HC might be mediated by the upregulation of antioxidant mechanisms and improved bioenergetics on the heart. Targeting bioenergetics with QUE can be used as a pharmacological approach to modulate structural and functional changes of the heart under hypercholesterolemic and hyperglycemic conditions.

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“…Improved diastolic function has also been observed after gene therapy with an adeno‐associated viral serotype 8 human apo A‐I vector in C57BL/6 LDL receptor‐deficient mice (Amin et al, ). In a model of cholesterol‐ and vitamin D2‐enriched diet‐induced mild aortic valve stenosis and left ventricular hypertrophy in rabbits, the HDL mimetic peptide CER‐522 improved echocardiographic indices of left ventricular diastolic dysfunction (Merlet et al, ).…”

Section: Discussionmentioning

confidence: 99%

Successful treatment of established heart failure in mice with recombinant HDL (Milano)

Aboumsallem

Mishra

Amin

et al. 2018

British J Pharmacology

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HDL mimetic peptide CER-522 treatment regresses left ventricular diastolic dysfunction in cholesterol-fed rabbits

Cited by 11 publications

References 38 publications

Cardiovascular organ damage in type 2 diabetes mellitus: the role of lipids and inflammation

Cardiovascular organ damage in type 2 diabetes mellitus: the role of lipids and inflammation

Quercetin Prevents Diastolic Dysfunction Induced by a High‐Cholesterol Diet: Role of Oxidative Stress and Bioenergetics in Hyperglycemic Rats

Successful treatment of established heart failure in mice with recombinant HDL (Milano)

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