Arteriogenic Therapy by Intramyocardial Sustained Delivery of a Novel Growth Factor Combination Prevents Chronic Heart Failure

Banquet, Sébastien; Gomez, Elodie; Nicol, Lionel; Edwards-Lévy, Florence; Henry, Jean‐Paul; Cao, Renhai; Schapman, Damien; Dautreaux, Brigitte; Lallemand, Françoise; Bauer, Fabrice; Cao, Yihai; Thuillez, Christian; Mulder, Paul; Richard, Vincent; Bråkenhielm, Ebba

doi:10.1161/circulationaha.110.010264

Cited by 78 publications

(66 citation statements)

References 46 publications

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“…27 Albumin-alginate microparticles, loaded or not with VEGF-C C152S , were injected in the LV free wall after reperfusion in the temporary MI model.…”

Section: Surgical Modelmentioning

confidence: 99%

“…27 MRI analyses were performed in anesthetized rats, as described, 27 and for T2-mapping of cardiac water content by using a 4.7T horizontal bore scanner (Bruker). Invasive hemodynamic assessment of cardiac function was performed by LV catheterization as previously described.…”

Section: Echocardiography Mri and Hemodynamicsmentioning

confidence: 99%

“…33 Our biodegradable, injectable albumin-alginate microparticles release bioactive growth factors, including VEGF-C C152S , over several weeks, as assessed in vitro (Figure VA through VC in the online-only Data Supplement), leading to increased therapeutic efficacy over naked protein delivery, and spatiotemporally controlled effects, as well, as demonstrated previously. 27 One of the many advantages of our microparticle-based approach is that it is associated with minimal immunological interference, as opposed to adenoviral therapy, which in addition may lead to lymphatic uptake and transport of active virions. 34 In contrast, our microparticles are small enough to be readily injectable, yet large enough to be entrapped between cardiomyocytes at the injection site, thus limiting spatially, in addition to temporally, the release of bioactive factors.…”

Section: Selective Stimulation Of Cardiac Lymphangiogenesis By Targetmentioning

confidence: 99%

“…Cardiac interstitial collagen density (fibrosis) in noninfarct areas was evaluated as described. 27 For details, see online-only Data Supplement Methods. …”

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confidence: 99%

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Selective Stimulation of Cardiac Lymphangiogenesis Reduces Myocardial Edema and Fibrosis Leading to Improved Cardiac Function Following Myocardial Infarction

et al. 2016

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Background-The lymphatic system regulates interstitial tissue fluid balance, and lymphatic malfunction causes edema.The heart has an extensive lymphatic network displaying a dynamic range of lymph flow in physiology. Myocardial edema occurs in many cardiovascular diseases, eg, myocardial infarction (MI) and chronic heart failure, suggesting that cardiac lymphatic transport may be insufficient in pathology. Here, we investigate in rats the impact of MI and subsequent chronic heart failure on the cardiac lymphatic network. Further, we evaluate for the first time the functional effects of selective therapeutic stimulation of cardiac lymphangiogenesis post-MI. Methods and Results-We investigated cardiac lymphatic structure and function in rats with MI induced by either temporary occlusion (n=160) or permanent ligation (n=100) of the left coronary artery. Although MI induced robust, intramyocardial capillary lymphangiogenesis, adverse remodeling of epicardial precollector and collector lymphatics occurred, leading to reduced cardiac lymphatic transport capacity. Consequently, myocardial edema persisted for several months post-MI, extending from the infarct to noninfarcted myocardium. Intramyocardial-targeted delivery of the vascular endothelial growth factor receptor 3-selective designer protein VEGF-C C152S , using albumin-alginate microparticles, accelerated cardiac lymphangiogenesis in a dose-dependent manner and limited precollector remodeling post-MI. As a result, myocardial fluid balance was improved, and cardiac inflammation, fibrosis, and dysfunction were attenuated. Conclusions-We show that, despite the endogenous cardiac lymphangiogenic response post-MI, the remodeling and dysfunction of collecting ducts contribute to the development of chronic myocardial edema and inflammationaggravating cardiac fibrosis and dysfunction. Moreover, our data reveal that therapeutic lymphangiogenesis may be a promising new approach for the treatment of cardiovascular diseases. deleterious effects, including induction of blood vascular rarefaction and dysfunction and stimulation of cardiac fibrosis, contributing to the development of chronic heart failure . 14 Furthermore, many inflammatory mediators, and oxygen radicals generated during inflammation, as well, negatively affect lymphatic function, causing impairment of lymph flow and initiation of lymph edema and chronic inflammation. 15,16 It is noteworthy that clinically detectable myocardial edema, extending beyond the infarct zone, may persist for up to 6 to 12 months post-myocardial infarction (MI) in humans, which is suggestive of lymphatic insufficiency. 17,18Whether cardiac lymphatic dysfunction occurs after myocardial injury, and the impact this may have on myocardial fluid balance and cardiac inflammation, remains to be investigated. Moreover, although the advent of molecular lymphatic markers has fueled investigations into lymphatic anatomy, function, and growth in many organs, 19-21 only a handful of articles have assessed lymphangiogenesis in the heart. It was rec...

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“…27 Albumin-alginate microparticles, loaded or not with VEGF-C C152S , were injected in the LV free wall after reperfusion in the temporary MI model.…”

Section: Surgical Modelmentioning

confidence: 99%

Section: Echocardiography Mri and Hemodynamicsmentioning

confidence: 99%

Section: Selective Stimulation Of Cardiac Lymphangiogenesis By Targetmentioning

confidence: 99%

“…Cardiac interstitial collagen density (fibrosis) in noninfarct areas was evaluated as described. 27 For details, see online-only Data Supplement Methods. …”

mentioning

confidence: 99%

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Selective Stimulation of Cardiac Lymphangiogenesis Reduces Myocardial Edema and Fibrosis Leading to Improved Cardiac Function Following Myocardial Infarction

et al. 2016

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“…A combination of fibroblast growth factor-2 and hepatocyte growth factor synergistically stimulated angiogenesis and prevented progression of heart failure in a rat model of MI. 84 To improve the efficacy and safety of the therapeutic interventions for myocardial angiogenesis, further studies are required to determine the optimal combination of angiogenic growth factors and to improve the technology of delivery methods to the myocardium.…”

Section: Therapeutic Myocardial Angiogenesis As a Potential Therapy Fmentioning

confidence: 99%

Angiogenesis and Cardiac Hypertrophy

Oka

Akazawa

Naito

et al. 2014

Circulation Research

373

178

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Cardiac hypertrophy is an adaptive response to physiological and pathological overload. In response to the overload, individual cardiac myocytes become mechanically stretched and activate intracellular hypertrophic signaling pathways to re-use embryonic transcription factors and to increase the synthesis of various proteins, such as structural and contractile proteins. These hypertrophic responses increase oxygen demand and promote myocardial angiogenesis to dissolve the hypoxic situation and to maintain cardiac contractile function; thus, these responses suggest crosstalk between cardiac myocytes and microvasculature. However, sustained pathological overload induces maladaptation and cardiac remodeling, resulting in heart failure. In recent years, specific understanding has increased with regard to the molecular processes and cell-cell interactions that coordinate myocardial growth and angiogenesis. In this review, we summarize recent advances in understanding the regulatory mechanisms of coordinated myocardial growth and angiogenesis in the pathophysiology of cardiac hypertrophy and heart failure. (Circ Res. 2014;114:565-571.)

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2019

Numerical Simulation, an Art of Prediction 1

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Arteriogenic Therapy by Intramyocardial Sustained Delivery of a Novel Growth Factor Combination Prevents Chronic Heart Failure

Cited by 78 publications

References 46 publications

Selective Stimulation of Cardiac Lymphangiogenesis Reduces Myocardial Edema and Fibrosis Leading to Improved Cardiac Function Following Myocardial Infarction

Selective Stimulation of Cardiac Lymphangiogenesis Reduces Myocardial Edema and Fibrosis Leading to Improved Cardiac Function Following Myocardial Infarction

Angiogenesis and Cardiac Hypertrophy

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