Improvement of contractility accompanies angiogenesis rather than arteriogenesis in chronic myocardial ischemia

Heilmann, Claudia; Kostic, Caterina; Giannone, Bodo; Grawitz, Andrea Busse; Armbruster, W.; Lutter, Georg; Beyersdorf, Friedhelm; Göbel, Heike

doi:10.1016/j.vph.2006.01.002

Cited by 6 publications

(4 citation statements)

References 23 publications

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“…(3, 4) This is important because an increased number of capillaries has been correlated with an increase in contractility and function under stress conditions. (5) Endogenous repair machinery is inadequate to correct this deficiency and tremendous resources have been devoted to developing molecular therapies that enhance both the microvascular perfusion and the function of ischemic or infarcted myocardium.…”

Section: Introductionmentioning

confidence: 99%

Myocardial tissue elastic properties determined by atomic force microscopy after stromal cell–derived factor 1α angiogenic therapy for acute myocardial infarction in a murine model

Hiesinger

Brukman

McCormick

et al. 2012

The Journal of Thoracic and Cardiovascular Surgery

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BACKGROUND Ventricular remodeling after myocardial infarction begins with massive extracellular matrix deposition and resultant fibrosis. This loss of functional tissue and the stiffening of myocardial elastic and contractile elements starts the vicious cycle of mechanical inefficiency, adverse remodeling, and eventual heart failure. We hypothesize that SDF-1α therapy to microrevascularize ischemic myocardium will rescue salvageable peri-infarct tissue and subsequently improve myocardial elasticity. METHODS Immediately following LAD ligation, mice were randomized to receive peri-infarct injection of either saline or SDF. After six weeks, the animals were sacrificed and samples were taken from the peri-infarct borderzone, the infarct scar, and the left ventricle of non-infarcted control mice. Determination of the tissues’ elastic moduli was carried out by mechanical testing in an atomic force microscope. RESULTS SDF treated peri-infarct tissue most closely approximated the elasticity of normal ventricle and was significantly more elastic than saline treated myocardium (109 + 22.9 kPa vs. 295 + 42.3 kPa, p < 0.0001). The myocardial scar, the strength of which depends on matrix deposition from vasculature at the peri-infarct edge, was stiffer in SDF treated animals when compared to controls (804 + 102.2 kPa vs. 144 + 27.5 kPa, p < 0.0001). CONCLUSIONS This study, through direct quantification of myocardial elastic properties, has demonstrated the ability of SDF to re-engineer the evolving myocardial infarct and peri-infarct tissue. By increasing the elasticity of the ischemic and dysfunctional peri-infarct borderzone and bolstering the weak aneurysm prone scar, SDF therapy may confer a mechanical advantage to resist adverse remodeling following infarction.

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Section: Introductionmentioning

confidence: 99%

Myocardial tissue elastic properties determined by atomic force microscopy after stromal cell–derived factor 1α angiogenic therapy for acute myocardial infarction in a murine model

Hiesinger

Brukman

McCormick

et al. 2012

The Journal of Thoracic and Cardiovascular Surgery

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show abstract

“…Additionally, conventional revascularization methods do not adequately address the microvascular destruction that accompanies a significant ischemic myocardial injury. 1–4 These factors have driven investigators to develop novel revascularization techniques that specifically target the microvasculature in ischemic myocardium. 5–7 …”

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confidence: 99%

Tissue-engineered pro-angiogenic fibroblast scaffold improves myocardial perfusion and function and limits ventricular remodeling after infarction

Fitzpatrick

Frederick

McCormick

et al. 2010

The Journal of Thoracic and Cardiovascular Surgery

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Objective Microvascular malperfusion after myocardial infarction leads to infarct expansion, adverse remodeling, and functional impairment. Native reparative mechanisms exist but are inadequate to vascularize ischemic myocardium. We hypothesized that a 3-dimensional human fibroblast culture (3DFC) functions as a sustained source of angiogenic cytokines, thereby augmenting native angiogenesis and limiting adverse effects of myocardial ischemia. Methods Lewis rats underwent ligation of the left anterior descending coronary artery to induce heart failure; experimental animals received a 3DFC scaffold to the ischemic region. Border-zone tissue was analyzed for the presence of human fibroblast surface protein, vascular endothelial growth factor, and hepatocyte growth factor. Cardiac function was assessed with echocardiography and pressure–volume conductance. Hearts underwent immunohistochemical analysis of angiogenesis by co-localization of platelet endothelial cell adhesion molecule and alpha smooth muscle actin and by digital analysis of ventricular geometry. Microvascular angiography was performed with fluorescein-labeled lectin to assess perfusion. Results Immunoblotting confirmed the presence of human fibroblast surface protein in rats receiving 3DFC, indicating survival of transplanted cells. Increased expression of vascular endothelial growth factor and hepatocyte growth factor in experimental rats confirmed elution by the 3DFC. Microvasculature expressing platelet endothelial cell adhesion molecule/alpha smooth muscle actin was increased in infarct and border-zone regions of rats receiving 3DFC. Microvascular perfusion was also improved in infarct and border-zone regions in these rats. Rats receiving 3DFC had increased wall thickness, smaller infarct area, and smaller infarct fraction. Echocardiography and pressure–volume measurements showed that cardiac function was preserved in these rats. Conclusions Application of a bioengineered 3DFC augments native angiogenesis through delivery of angiogenic cytokines to ischemic myocardium. This yields improved microvascular perfusion, limits infarct progression and adverse remodeling, and improves ventricular function.

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“…For these same reasons, the duration of release of MCP-1 was significantly less than that previously reported for VEGF in the same particle system [7, 30]. Interestingly, short-term expression of MCP-1 has been shown to lead to improved reperfusion in a hindlimb ischemia model [34] while a longer duration of expression yielded no therapeutic benefit in conjunction with FGF-2 delivery [35] despite the established relationship between these two factors [36]. Therefore, it is reasonable to conclude that the duration of release of MCP-1 exhibited by these scaffolds could lead to the therapeutic effects observed in this study.…”

Section: Discussionmentioning

confidence: 99%

Dual delivery of VEGF and MCP-1 to support endothelial cell transplantation for therapeutic vascularization

et al. 2010

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Transplantation of endothelial cells (EC) for therapeutic vascularization is a promising approach in tissue engineering but has yet to be proven effective in clinical trials. This cell-based therapy is hindered by significant apoptosis of EC upon transplantation as well as poor recruitment of host mural cells to stabilize nascent vessels. Here, we address these deficiencies by augmenting endothelial cell transplantation with dual delivery of vascular endothelial growth factor (VEGF) – to improve survival of transplanted EC – and monocyte chemotactic protein-1 (MCP-1) – to induce mural cell recruitment. We produced alginate microparticles that deliver VEGF and MCP-1 with distinct release kinetics and that can be integrated into a collagen/fibronectin (protein) gel construct for delivery of EC. Combined delivery of VEGF and MCP-1 increased functional vessel formation from transplanted EC and also led to a higher number of smooth muscle cell-invested vessels than did EC therapy alone. Despite the well-known role of MCP-1 in inflammation, these beneficial effects were accomplished without a long-term increase in monocyte/macrophage recruitment or a shift to a pro-inflammatory (M1) macrophage phenotype. Overall, these data suggest a potential benefit of combined delivery of MCP-1 and VEGF from EC-containing hydrogels as a strategy for therapeutic vascularization.

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Improvement of contractility accompanies angiogenesis rather than arteriogenesis in chronic myocardial ischemia

Cited by 6 publications

References 23 publications

Myocardial tissue elastic properties determined by atomic force microscopy after stromal cell–derived factor 1α angiogenic therapy for acute myocardial infarction in a murine model

Myocardial tissue elastic properties determined by atomic force microscopy after stromal cell–derived factor 1α angiogenic therapy for acute myocardial infarction in a murine model

Tissue-engineered pro-angiogenic fibroblast scaffold improves myocardial perfusion and function and limits ventricular remodeling after infarction

Dual delivery of VEGF and MCP-1 to support endothelial cell transplantation for therapeutic vascularization

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