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Improving reconstituted HDL composition for efficient post-ischemic reduction of ischemia reperfusion injury.

Brulhart-Meynet MC, Braunersreuther V, Brinck J, Montecucco F, Prost JC, Thomas A, Galan K, Pelli G, Pedretti S, Vuilleumier N, Mach F, Lecour S, James RW, Frias MA - PLoS ONE (2015)

Bottom Line: Acute post-ischemic treatment with native HDL significantly reduced infarct size and cell death in the ex vivo, isolated heart (Langendorff) model and the in vivo model (-48%, p<0.01).This impact was comparable with the effects observed with native HDL.HDL afford protection against IRI in a clinically relevant model (post-ischemia). rHDL is significantly protective if supplemented with S1P.

View Article: PubMed Central - PubMed

Affiliation: Service of Endocrinology, Diabetology, Hypertension and Nutrition, Department of Internal Medicine, Faculty of Medicine, Geneva, Switzerland.

ABSTRACT

Background: New evidence shows that high density lipoproteins (HDL) have protective effects beyond their role in reverse cholesterol transport. Reconstituted HDL (rHDL) offer an attractive means of clinically exploiting these novel effects including cardioprotection against ischemia reperfusion injury (IRI). However, basic rHDL composition is limited to apolipoprotein AI (apoAI) and phospholipids; addition of bioactive compound may enhance its beneficial effects.

Objective: The aim of this study was to investigate the role of rHDL in post-ischemic model, and to analyze the potential impact of sphingosine-1-phosphate (S1P) in rHDL formulations.

Methods and results: The impact of HDL on IRI was investigated using complementary in vivo, ex vivo and in vitro IRI models. Acute post-ischemic treatment with native HDL significantly reduced infarct size and cell death in the ex vivo, isolated heart (Langendorff) model and the in vivo model (-48%, p<0.01). Treatment with rHDL of basic formulation (apoAI + phospholipids) had a non-significant impact on cell death in vitro and on the infarct size ex vivo and in vivo. In contrast, rHDL containing S1P had a highly significant, protective influence ex vivo, and in vivo (-50%, p<0.01). This impact was comparable with the effects observed with native HDL. Pro-survival signaling proteins, Akt, STAT3 and ERK1/2 were similarly activated by HDL and rHDL containing S1P both in vitro (isolated cardiomyocytes) and in vivo.

Conclusion: HDL afford protection against IRI in a clinically relevant model (post-ischemia). rHDL is significantly protective if supplemented with S1P. The protective impact of HDL appears to target directly the cardiomyocyte.

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Related in: MedlinePlus

rHDL containing S1P protect against ischemia reperfusion injury ex vivo.Isolated hearts were submitted to global ischemia (35min) followed by reperfusion (45min). At the onset of reperfusion, hearts were treated or not (control) with native HDL (nHDL), rHDL (apoAI+POPC) or rHDLB (apoAI + POPC + S1P) during the first 7min. Infarct size is expressed as percentage of total heart area, (mean±SEM). ***p<0.001 vs control using one-way ANOVA combined with Tukey multiple comparisons post-hoc test, n≥4.
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pone.0119664.g003: rHDL containing S1P protect against ischemia reperfusion injury ex vivo.Isolated hearts were submitted to global ischemia (35min) followed by reperfusion (45min). At the onset of reperfusion, hearts were treated or not (control) with native HDL (nHDL), rHDL (apoAI+POPC) or rHDLB (apoAI + POPC + S1P) during the first 7min. Infarct size is expressed as percentage of total heart area, (mean±SEM). ***p<0.001 vs control using one-way ANOVA combined with Tukey multiple comparisons post-hoc test, n≥4.

Mentions: Analysis of the impact of rHDL on IRI in the isolated heart allowed us to eliminate potentially confounding, systemic, anti-inflammatory effects of HDL (for protocol details see Fig. 1A). Native HDL was used as a positive control. As shown in Fig. 3, native HDL reduced infarct size by 31.7%±3.9 (p<0.001). With respect to rHDL, treatment with basic rHDL (POPC+apoAI) did not significantly reduce infarct size (p = 0.056). Corresponding to the results observed in vitro, addition of S1P to basic rHDL resulted in a highly significant reduction in infarct size (Fig. 3; p<0.001), similar to that observed for native HDL.


Improving reconstituted HDL composition for efficient post-ischemic reduction of ischemia reperfusion injury.

Brulhart-Meynet MC, Braunersreuther V, Brinck J, Montecucco F, Prost JC, Thomas A, Galan K, Pelli G, Pedretti S, Vuilleumier N, Mach F, Lecour S, James RW, Frias MA - PLoS ONE (2015)

rHDL containing S1P protect against ischemia reperfusion injury ex vivo.Isolated hearts were submitted to global ischemia (35min) followed by reperfusion (45min). At the onset of reperfusion, hearts were treated or not (control) with native HDL (nHDL), rHDL (apoAI+POPC) or rHDLB (apoAI + POPC + S1P) during the first 7min. Infarct size is expressed as percentage of total heart area, (mean±SEM). ***p<0.001 vs control using one-way ANOVA combined with Tukey multiple comparisons post-hoc test, n≥4.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4362758&req=5

pone.0119664.g003: rHDL containing S1P protect against ischemia reperfusion injury ex vivo.Isolated hearts were submitted to global ischemia (35min) followed by reperfusion (45min). At the onset of reperfusion, hearts were treated or not (control) with native HDL (nHDL), rHDL (apoAI+POPC) or rHDLB (apoAI + POPC + S1P) during the first 7min. Infarct size is expressed as percentage of total heart area, (mean±SEM). ***p<0.001 vs control using one-way ANOVA combined with Tukey multiple comparisons post-hoc test, n≥4.
Mentions: Analysis of the impact of rHDL on IRI in the isolated heart allowed us to eliminate potentially confounding, systemic, anti-inflammatory effects of HDL (for protocol details see Fig. 1A). Native HDL was used as a positive control. As shown in Fig. 3, native HDL reduced infarct size by 31.7%±3.9 (p<0.001). With respect to rHDL, treatment with basic rHDL (POPC+apoAI) did not significantly reduce infarct size (p = 0.056). Corresponding to the results observed in vitro, addition of S1P to basic rHDL resulted in a highly significant reduction in infarct size (Fig. 3; p<0.001), similar to that observed for native HDL.

Bottom Line: Acute post-ischemic treatment with native HDL significantly reduced infarct size and cell death in the ex vivo, isolated heart (Langendorff) model and the in vivo model (-48%, p<0.01).This impact was comparable with the effects observed with native HDL.HDL afford protection against IRI in a clinically relevant model (post-ischemia). rHDL is significantly protective if supplemented with S1P.

View Article: PubMed Central - PubMed

Affiliation: Service of Endocrinology, Diabetology, Hypertension and Nutrition, Department of Internal Medicine, Faculty of Medicine, Geneva, Switzerland.

ABSTRACT

Background: New evidence shows that high density lipoproteins (HDL) have protective effects beyond their role in reverse cholesterol transport. Reconstituted HDL (rHDL) offer an attractive means of clinically exploiting these novel effects including cardioprotection against ischemia reperfusion injury (IRI). However, basic rHDL composition is limited to apolipoprotein AI (apoAI) and phospholipids; addition of bioactive compound may enhance its beneficial effects.

Objective: The aim of this study was to investigate the role of rHDL in post-ischemic model, and to analyze the potential impact of sphingosine-1-phosphate (S1P) in rHDL formulations.

Methods and results: The impact of HDL on IRI was investigated using complementary in vivo, ex vivo and in vitro IRI models. Acute post-ischemic treatment with native HDL significantly reduced infarct size and cell death in the ex vivo, isolated heart (Langendorff) model and the in vivo model (-48%, p<0.01). Treatment with rHDL of basic formulation (apoAI + phospholipids) had a non-significant impact on cell death in vitro and on the infarct size ex vivo and in vivo. In contrast, rHDL containing S1P had a highly significant, protective influence ex vivo, and in vivo (-50%, p<0.01). This impact was comparable with the effects observed with native HDL. Pro-survival signaling proteins, Akt, STAT3 and ERK1/2 were similarly activated by HDL and rHDL containing S1P both in vitro (isolated cardiomyocytes) and in vivo.

Conclusion: HDL afford protection against IRI in a clinically relevant model (post-ischemia). rHDL is significantly protective if supplemented with S1P. The protective impact of HDL appears to target directly the cardiomyocyte.

Show MeSH
Related in: MedlinePlus