Monocyte Modulation by Liposomal Alendronate Improves Cardiac Healing in a Rat Model of Myocardial Infarction

Grad, Etty; Gutman, Dikla; Golomb, Mordechai; Efraim, Roi; Oppenheim, Amit; Richter, Ilan; Danenberg, Haim; Golomb, Gershon

doi:10.1007/s40883-019-00103-8

Cited by 3 publications

(4 citation statements)

References 46 publications

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“…In addition, PR1P therapy led to improved cardiac contractility as indicated by an increase in the fractional change in area ( Figure 2 C) and increased left ventricular shortening fraction ( Figure 2 D). Representative photomicrographs of Masson trichrome stained cross sections of myocardium (to identify collagen at sites of infarction [ 16 ]) from PR1P- and SP-treated rats 14 days after coronary artery ligation surgery are shown in Figure 2 E–F. Quantification of the infarct sizes from micrographs in similarly stained heart sections show decreased areas of infarction at both 3 and 14 days from surgery ( Figure 2 G–H).…”

Section: Resultsmentioning

confidence: 99%

“…Heart sections (4 μm) were treated with Masson’s trichrome (MTC, Thermo Scientific, Rockford, IL, USA), which stains collagen blue and myocardial cells pink red. Photomicrographs of sections of the left ventricle were used to quantify myocardial infarction size as described by Grad et al [ 16 ]. Briefly, infarct size was calculated as a normalized ratio of the minimal width of the infarcted area compared to the area of the left ventricle (LV) muscle area ((min width × 100)/LV Area, i.e., blue stain)/total LV muscle area (cm 2 ), as well as a normalized ratio of the infarct area to the whole left ventricle area ((Infarct Area × 100)/LV area) using ImageJ© software (National Institute of Health, Bethesda, MD, USA).…”

Section: Methodsmentioning

confidence: 99%

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The Prominin-1-Derived Peptide Improves Cardiac Function Following Ischemia

Adini

Grad

et al. 2021

IJMS

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Myocardial infarction (MI) remains the leading cause of death in the western world. Despite advancements in interventional revascularization technologies, many patients are not candidates for them due to comorbidities or lack of local resources. Non-invasive approaches to accelerate revascularization within ischemic tissues through angiogenesis by providing Vascular Endothelial Growth Factor (VEGF) in protein or gene form has been effective in animal models but not in humans likely due to its short half-life and systemic toxicity. Here, we tested the hypothesis that PR1P, a small VEGF binding peptide that we developed, which stabilizes and upregulates endogenous VEGF, could be used to improve outcome from MI in rodents. To test this hypothesis, we induced MI in mice and rats via left coronary artery ligation and then treated animals with every other day intraperitoneal PR1P or scrambled peptide for 14 days. Hemodynamic monitoring and echocardiography in mice and echocardiography in rats at 14 days showed PR1P significantly improved multiple functional markers of heart function, including stroke volume and cardiac output. Furthermore, molecular biology and histological analyses of tissue samples showed that systemic PR1P targeted, stabilized and upregulated endogenous VEGF within ischemic myocardium. We conclude that PR1P is a potential non-invasive candidate therapeutic for MI.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

The Prominin-1-Derived Peptide Improves Cardiac Function Following Ischemia

Adini

Grad

et al. 2021

IJMS

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show abstract

“…Heart sections (4 m) were treated with Masson's trichrome (MTC, Thermo Scientific, Rockford, IL), which stains collagen blue and myocardial cells pink red. Photomicrographs of sections of the left ventricle were used to quantify myocardial infarction size as described by Grad et al 14 Briefly, infarct size was calculated as a normalized ratio of the minimal width of the infarcted area compared to the area of the left ventricle (LV) muscle area ((min width * 100)/LV Area, i.e. blue stain)/total LV muscle area (cm 2 ), as well as a normalized ratio of the infarct area to the whole left ventricle area ((Infarct Area *100)/LV area) using ImageJ© software (National Institute of Health, Bethesda, MD).…”

Section: Histology and Immunochemistry (Rat Heart Infarct Quantification)mentioning

confidence: 99%

“…2D). Representative photomicrographs of Masson trichrome stained cross sections of myocardium (to identify collagen at sites of infarction 14 ) from PR1P and SP treated rats 14 days after coronary artery ligation surgery are shown in Fig. 2E-F.…”

Section: Pr1p Improves Murine Myocardial Function Post-infarctionmentioning

confidence: 99%

The Prominin-1 Derived Peptide Improves Cardiac Function Following Ischemia

Adini

Grad

et al. 2021

Preprint

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Myocardial infarction (MI) remains the leading cause of death in the western world. Although medical advancements have been made in interventional revascularization technologies, a large percentage of patients are not candidates for them due to co-morbidities or lack of local resources. Thus, there remains a need for the development of novel non-invasive strategies to treat MI. Approaches to accelerate revascularization within ischemic tissues through angiogenesis by providing Vascular Endothelial Growth Factor (VEGF) in protein or gene form has been shown to be effective in animal models but not in humans likely due to its short half-life and systemic toxicity. We previously showed that a small peptide (PR1P) we developed stabilizes VEGF in its active dimer state, increases VEGF binding to its receptors and potentiates VEGF activity. Here we show that systemic PR1P treatment targeted, stabilized and upregulated endogenous VEGF within ischemic myocardium following left coronary artery surgery in mice and rats. Targeted VEGF upregulation led to augmentation of heart function at two weeks following surgery. We conclude that PR1P is a potential candidate therapeutic for MI.

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