Hypercholesterolemia Abolishes High-Density Lipoprotein–Related Cardioprotective Effects in the Setting of Myocardial Infarction

Vilahur, Gemma; Gutiérrez, Manuel; Casaní, Laura; Cubedo, Judit; Capdevila, Antoni; Pons-Lladó, Ġuillem; Carreras, Francesc; Hidalgo, Alberto; Badimon, Lina

doi:10.1016/j.jacc.2015.08.901

Cited by 35 publications

(27 citation statements)

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“…MI was induced by 90-min total balloon occlusion of the LAD as described previously [25]. All animals underwent transthoracic echocardiography before inducing ischemia and upon reperfusion to monitor the impact of MI induction on LVEF [26].…”

Section: Methodsmentioning

confidence: 99%

“…CMR analysis was performed serially as reported previously [25] 1 week post MI just after ASC, CM, ASC + CM or PBS infusion (baseline), 1 week post infusion (2 weeks post MI) and 3 weeks post infusion (4 weeks post MI). The following CMR sequences were acquired: “cine” (b-SSFP) imaging sequence to assess wall motion and cardiac function; and late gadolinium enhancement (LGE) to assess the amount and extent of myocardial necrosis.…”

Section: Methodsmentioning

confidence: 99%

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Allogenic adipose-derived stem cell therapy overcomes ischemia-induced microvessel rarefaction in the myocardium: systems biology study

et al. 2017

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BackgroundMyocardial microvascular loss after myocardial infarction (MI) remains a therapeutic challenge. Autologous stem cell therapy was considered as an alternative; however, it has shown modest benefits due to the impairing effects of cardiovascular risk factors on stem cells. Allogenic adipose-derived stem cells (ASCs) may overcome such limitations, and because of their low immunogenicity and paracrine potential may be good candidates for cell therapy. In the present study we investigated the effects of allogenic ASCs and their released products on cardiac rarefaction post MI.MethodsPig subcutaneous adipose tissue ASCs were isolated, expanded and GFP-labeled. ASC angiogenic function was assessed by the in-vivo chick chorioallantoic membrane (CAM) model. Pigs underwent MI induction and 7 days after were randomized to receive: allogenic ASCs (intracoronary infusion); conditioned media (CM; intravenous infusion); ASCs + CM; or PBS/placebo (control). Cardiac damage and function were monitored by 3-T cardiac magnetic resonance imaging upon infusion (baseline CMR) and 1 and 3 weeks thereafter. We assessed in the myocardium: microvessel density; angiogenic markers (CD105, CD31, TF, VEGFR2, VEGFR1, vWF, eNOS, CD62); collagen deposition; and reparative fibrosis (TGFβ/TβRII/collagen). Differential proteomics of ASCs and CM was performed to characterize the ASC protein signature.ResultsCAM indicated a significant ASC proangiogenic capacity. In pigs after MI, only PBS/placebo animals displayed an impaired cardiac function 3 weeks after infusion (p < 0.05 vs baseline). Administration of ASCs + CM significantly enhanced neovessel formation and favored cardiac repair post MI (p < 0.05 vs the other groups). Molecular markers of angiogenesis were significantly upregulated both at transcriptional and protein levels (p < 0.05). The in-silico bioinformatics analysis of the ASC and CM proteome (interactome) indicated activation of a coordinated protein network involved in the formation of microvessels and the resolution of rarefaction.ConclusionCoadministration of allogenic ASCs and their CM synergistically contribute to the neovascularization of the infarcted myocardium through a coordinated upregulation of the proangiogenic protein interactome.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0509-2) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Allogenic adipose-derived stem cell therapy overcomes ischemia-induced microvessel rarefaction in the myocardium: systems biology study

et al. 2017

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“…194 Also, pretreatment with high-density lipoproteins from normocholesterolemic pigs which contain a load of sphingosine-1-phosphate 195 reduced infarct size and the extent of no-reflow in pigs. 196 Pretreatment with simvastatin reduced infarct size and the area of no-reflow in pigs, and such protection was related to activation of protein kinase A 197 and of mitochondrial ATPdependent potassium channels. 198 Glucagon-like peptide 1 when given just before reperfusion in rats decreased infarct size and reduced the accumulation of leukocytes in the reperfused myocardium.…”

Section: Drugsmentioning

confidence: 97%

The Coronary Circulation as a Target of Cardioprotection

Heusch

2016

Circulation Research

209

160

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Abstract:The atherosclerotic coronary vasculature is not only the culprit but also a victim of myocardial ischemia/ reperfusion injury. Manifestations of such injury are increased vascular permeability and edema, endothelial dysfunction and impaired vasomotion, microembolization of atherothrombotic debris, stasis with intravascular cell aggregates, and finally, in its most severe form, capillary destruction with hemorrhage. In animal experiments, local and remote ischemic pre-and postconditioning not only reduce infarct size but also these manifestations of coronary vascular injury, as do drugs which recruit signal transduction steps of conditioning. Clinically, no-reflow is frequently seen after interventional reperfusion, and it carries an adverse prognosis. The translation of cardioprotective interventions to clinical practice has been difficult to date. Only 4 drugs (brain natriuretic peptide, exenatide, metoprolol, and esmolol) stand unchallenged to date in reducing infarct size in patients with reperfused acute myocardial infarction; unfortunately, for these drugs, no information on their impact on the ischemic/reperfused coronary circulation is available. (Circ Res.

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“…In primary prevention, high levels of LDL-cholesterol (LDL-C) are related with a higher incidence of cardiovascular events in the continuum of CVD, whereas HDL-cholesterol (HDL-C) levels are commonly known as a risk-reducing factor [9]. It is now accepted that the importance of HDL in the progression of CVD, resides on their quality rather than their quantity, highlighting the importance of their composition, structure, and function [10,11,12,13]. Indeed, apolipoprotein A–I (Apo A–I), the major protein component of HDL, has cardiovascular protective properties [14,15].…”

Section: Introductionmentioning

confidence: 99%

Phytosterols and Omega 3 Supplementation Exert Novel Regulatory Effects on Metabolic and Inflammatory Pathways: A Proteomic Study

Lambert¹,

Cubedo

Padró

et al. 2017

Nutrients

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Cardiovascular disease (CVD) remains one of the major causes of death and disability worldwide. In addition to drug treatment, nutritional interventions or supplementations are becoming a health strategy for CVD prevention. Phytosterols (PhyS) are natural components that have been shown to reduce cholesterol levels; while poly-unsaturated fatty acids (PUFA), mainly omega-3 (ω3) fatty acids, have shown to reduce triglyceride levels. Here we aimed to investigate whether the proteins in the main lipoproteins (low density lipoproteins (LDL) and high density lipoproteins (HDL)) as well as proteins in the lipid free plasma fraction (LPDP) were regulated by the intake of PhyS-milk or ω3-milk, in overweight healthy volunteers by a proteomic based systems biology approach. The study was a longitudinal crossover trial, including thirty-two healthy volunteers with body mass index (BMI) 25–35 kg/m2 (Clinical Trial: ISRCTN78753338). Basal samples before any intervention and after 4 weeks of intake of PhyS or ω3-milk were analyzed. Proteomic profiling by two dimensional electrophoresis (2-DE) followed by mass spectrometry-(MALDI/TOF), ELISA, Western blot, conventional biochemical analysis, and in-silico bioinformatics were performed. The intake of PhyS-milk did not induce changes in the lipid associated plasma protein fraction, whereas ω3-milk significantly increased apolipoprotein (Apo)- E LDL content (p = 0.043) and induced a coordinated increase in several HDL-associated proteins, Apo A–I, lecitin cholesterol acyltransferase (LCAT), paraoxonase-1 (PON-1), Apo D, and Apo L1 (p < 0.05 for all). Interestingly, PhyS-milk intake induced a reduction in inflammatory molecules not seen after ω3-milk intake. Serum amyloid P component (SAP) was reduced in the LPDP protein fraction (p = 0.001) of subjects taking PhyS-milk and C-C motif chemokine 2 (CCL2)expression detected by reverse transcription polymerase chain reaction (RT-PCR) analysis in white blood cells was significantly reduced (p = 0.013). No changes were observed in the lipid-free plasma proteome with ω3-milk. Our study provides novel results and highlights that the PhyS-milk induces attenuation of the pro-inflammatory pathways, whereas ω3-milk induces improvement in lipid metabolic pathways.

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Hypercholesterolemia Abolishes High-Density Lipoprotein–Related Cardioprotective Effects in the Setting of Myocardial Infarction

Cited by 35 publications

References 5 publications

Allogenic adipose-derived stem cell therapy overcomes ischemia-induced microvessel rarefaction in the myocardium: systems biology study

Allogenic adipose-derived stem cell therapy overcomes ischemia-induced microvessel rarefaction in the myocardium: systems biology study

The Coronary Circulation as a Target of Cardioprotection

Phytosterols and Omega 3 Supplementation Exert Novel Regulatory Effects on Metabolic and Inflammatory Pathways: A Proteomic Study

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