Impact of multivessel versus single-vessel disease on the association between low diastolic blood pressure and mortality after acute myocardial infarction with revascularization

Background: Previous studies demonstrated a J-shaped relationship between low diastolic blood pressure (DBP) and adverse clinical outcomes in patients with acute myocardial infarction (AMI) that was sensitive to revascularization. Hypothesized herein, was that this relationship differs between patients with multivessel disease (MVD) and those with single-vessel disease due to differing degrees of myocardial ischemic burden. Methods: Among 9,983 AMI patients from the Korea Acute Myocardial Infarction Registry database who underwent percutaneous coronary intervention and were followed up for a median duration of 3.2 years, average on-treatment DBP was calculated at admission, discharge, and every scheduled visit and divided into these parameters: < 70 mmHg, 70–74 mmHg, 75–79 mmHg, and ≥ 80 mmHg. The relationship between average on-treatment DBP and clinical outcomes including all-cause death, cardiovascular (CV) death, non-CV death, and hospitalization for heart failure was analyzed using the Cox regression models adjusted for clinical covariates. Results: In patients with MVD, all-cause death (hazard ratio [HR]: 1.47; 95% confidence interval [CI]: 1.06–2.04, p = 0.012) and CV death (HR: 1.59; 95% CI: 1.02–2.46, p = 0.027) were significantly increased in patients with a DBP < 70 mmHg, showing a J-shaped relationship. However, these findings were not significant for single-vessel disease. On a sensitivity analysis excluding subjects with a baseline SBP < 120 mmHg, an increased risk of a low DBP < 70 mmHg remained in MVD. Conclusions: The J-shaped relationship between low DBP and adverse clinical outcomes in AMI patients who underwent revascularization persisted in MVD, which has a high ischemic burden. These high-risk patients require cautious treatment

Biomimetic RGD-engineered elastin-like extracellular matrix facilitates cutaneous wound healing in C57BL/6 mice by way of promoting the migration of epidermal keratinocytes and dermal fibroblasts

Elastin-like proteins (ELPs) modeled after tropoelastin are emerged in the development of biomimetic matrices due to their biocompatibility and the possibility to precisely control their environmental responsiveness and mechanical properties. Integrins which were trans-membrane receptors known to mediate dynamic interactions for cellular movement binds to specific RGD motifs of ECM proteins such as fibronectin, collagen and laminin. To facilitate integrin-related bindings between cell and extra cellular matrix, we biosynthesized a modular Elastin-like proteins (ELPs), represented as TGPG[VGRGD(VGVPG)6]20WPC (RGD-ELP), consisting of elastic (VGVPG)6 structural domains and cell-binding VGRGD motifs. To evaluate the effect of RGD-ELP on tissue regeneration in vivo, we performed wound healing experiment using male C57BL/6 mice. We observed the notably accelerated wound closure in gross observation and promoted wound repair showing decreased area of granulation tissue and enhanced collagen formation by RGD-ELP treatment. Furthermore, RGD-ELP up-regulated the expression of α-smooth muscle actin (α-SMA) in granulation tissue of wounds and the expression level of E-cadherin in the epidermis. In in vitro wound healing assay using fibroblasts and keratinocytes, the migration of cells was significantly promoted on RGD-ELP-coated plates compared with non-coated plates. On the basis of these physiological and pathological changes, we concluded that RGD-ELP facilitates wound healing processes by way of promoting the migration of epidermal keratinocytes and dermal fibroblasts and enhancing the synthesis of collagen fibers and α-SMA. Thus, RGD-ELP is believed to be used as an elastin-like matrix of a therapeutic agent for wound healing.1

Morphogenetic and neuronal characterization of human neuroblastoma multicellular spheroids cultured under undifferentiated and all-trans-retinoic acid-differentiated conditions

In this study, we aimed to compare the morphogenetic andneuronal characteristics between monolayer cells andspheroids. For this purpose, we established spheroid formationby growing SH-SY5Y cells on the hydrophobic surfaces ofthermally-collapsed elastin-like polypeptide. After 4 days ofculture, the relative proliferation of the cells within spheroidswas approximately 92% of the values for monolayer cultures.As measured by quantitative assays for mRNA and proteinexpressions, the production of synaptophysin and neuronspecificenolase (NSE) as well as the contents of cell adhesionmolecules (CAMs) and extracellular matrix (ECM) proteins aremuch higher in spheroids than in monolayer cells. Under theall-trans-retinoic acid (RA)-induced differentiation condition,spheroids extended neurites and further up-regulated theexpression of synaptophysin, NSE, CAMs, and ECM proteins.Our data indicate that RA-differentiated SH-SY5Y neurospheroidsare functionally matured neuronal architectures. [BMBReports 2013; 46(5): 276-281

Effects of Arg-Gly-Asp-modified elastin-like polypeptide on pseudoislet formation via up-regulation of cell adhesion molecules and extracellular matrix proteins

Extracellular matrix (ECM) plays an important role in controlling the β-cell morphology, survival and insulin secretary functions. An RGD-modified elastin-like polypeptide (RGD-ELP), TGPG[VGRGD(VGVPG) 6]20WPC, has been reported previously as a bioactive matrix. In this study, to investigate whether RGD-ELP affects β-cell growth characteristics and insulin secretion, β-TC6 cells were cultured on the RGD-ELP coatings prepared via thermally induced phase transition. On RGD-ELP, β-TC6 cells clustered into an islet-like architecture with high cell viability. Throughout 7 days' culture, the proliferation rate of the cells within a pseudoislet was similar to that of monolayer culture. Under high glucose (25 mM), β-TC6 pseudoislets showed up-regulated insulin gene expression and exhibited glucose-stimulated insulin secretion. Importantly, the mRNA and protein abundances of cell adhesion molecules (CAM) E-cadherin and connexin-36 were much higher in pseudoislets than in monolayer cells. The siRNA-mediated inhibition of E-cadherin or connexin-36 expression severely limited pseudoislet formation. In addition, the mRNA levels of collagen types I and IV, fibronectin and laminin were significantly elevated in pseudoislets. The results suggest that RGD-ELP promotes pseudoislet formation via up-regulation of the CAM and ECM components. The functional roles of RGD-ELP are discussed in respect of its molecular composition. © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.1