Expression of α and β integrins during terminal differentiation of cardiomyocytes

Maitra, Niranjan; Flink, Irwin L.; Bahl, Joseph J.; Morkin, Eugene

doi:10.1016/s0008-6363(00)00140-1

Cited by 65 publications

(53 citation statements)

References 44 publications

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“…In their studies, Ang1 and VEGF were found to mediate endothelial cell adhesion and survival through interactions with integrins. 11,12 Since various kinds of integrins had been proved to express in adult myocardium, 13 interaction of integrins with VEGF 165 or Ang1 might be the first step that VEGF 165 or Ang1 activated the intracellular PI-3K pathway. Integrins can be served as adhesion receptors that transduce biochemical signals into the cell.…”

Section: Discussionmentioning

confidence: 99%

VEGF165 and angiopoietin-1 decreased myocardium infarct size through phosphatidylinositol-3 kinase and Bcl-2 pathways

Zhou

Yang

et al. 2004

Gene Ther

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Angiogenic growth factors, vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang1) could decrease myocardial infarct size, which was assumed to be related with newly formed capillaries. We doubted that these capillaries could do this solely and the potential protective mechanisms of VEGF and Ang1 on myocardium need to be evaluated. Three types of adenoviruses encoding human VEGF 165 (Ad-VEGF 165 ), human angiopoietin-1 (Ad-Ang1) and green fluorescent protein (Ad-GFP, as a parallel control) were constructed. Experiments were taken both in vitro and in vivo. As in vitro, the antiapoptosis effect of VEGF 165 , Ang1 and VEGF 165 +Ang1 on cardiac myoblasts was observed, which seemed to be related with the activation of phosphatidylinositol-3 kinase and Bcl-2 pathways. As in vivo, adenoviruses were intramyocardially injected immediately after the ligation of the left anterior descending coronay arteries in rats. The results showed positive effect of VEGF 165 , Ang1 and VEGF 165 +Ang1 on decreasing the myocardial infarct size at the 7th day. Myocardial PI-3K activity and Bcl-2 expression were elevated relatively at the 3rd day. The protective effect of VEGF 165 and Ang1 on the myocardium may broaden their functional research and contribute to their clinical use in the future.

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Section: Discussionmentioning

confidence: 99%

VEGF165 and angiopoietin-1 decreased myocardium infarct size through phosphatidylinositol-3 kinase and Bcl-2 pathways

Zhou

Yang

et al. 2004

Gene Ther

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“…␣ 6 is vital to CM function, prevalent on CM, and is not expressed by cardiac fibroblasts. 65 Isoforms (␣ 6A and ␣ 6B ) are expressed in fetal and adult hearts, 36 and levels shift during cardiac development. 66,67 The blocking effects of ␤ 3 and ␣ 6 antibodies support a link between myocyte-Ang1 interactions and activation of cell signaling (Figures 6 through 12).…”

Section: Dallabrida Et Al Angiopoietin-1 Promotes Myocyte Survival E15mentioning

confidence: 99%

“…34 Integrins are also regulated by dynamic spatial and temporal expression patterns 35 and subunit isoforms. For example, integrin adhesion, expression, and activation shift during cardiac development, 36 hypertrophy, 35 infarct, 37 and failure. 38 Information traffic via integrins is bidirectional, enabling cells to interact with the extracellular matrix (ECM)/environment.…”

mentioning

confidence: 99%

Angiopoietin-1 Promotes Cardiac and Skeletal Myocyte Survival Through Integrins

Dallabrida

Ismail²,

Oberle³

et al. 2005

Circulation Research

178

179

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Abstract-Cardiac myocyte loss, regardless of insult, can trigger compensatory myocardial remodeling leading to heart failure. Identifying mediators of cardiac myocyte survival may advance clinical efforts toward myocardial preservation. Angiopoietin-1 limits ischemia-induced cardiac injury. This benefit is ascribed to angiogenesis because the receptor, tie2, is largely endothelial-specific. We propose that direct, non-tie2 interactions of angiopoietin-1 on cardiac myocytes contribute to this cardioprotection. We found that mouse C2C12 skeletal myocytes lack tie2, yet dose-dependently adhered to angiopoietin-1 and angiopoietin-2 similarly to laminin, fibronectin, vitronectin, and more than to collagen-I, -III, and -IV. Adhesion was divalent cation-mediated (Mn 2ϩ , Ca 2ϩ , not Mg 2ϩ ), blocked with EDTA/EGTA, RGD-based peptides, and select integrin subunit antibodies. Similar findings were obtained with human skeletal myocytes (HSMs) and freshly isolated rat neonatal cardiac myocytes (NCMs). Furthermore, angiopoietin-1 conferred significant survival advantage exceeding that of most cell matrices, which was not fully explained by differences in cell adhesion. Angiopoietin-1 promoted survival of serum-starved C2C12, HSM, and NCM (MTT, trypan blue) and prevented taxol-induced apoptosis (caspase-3). Immobilized and soluble angiopoietin-1 phosphorylated Akt S473 and MAPK p42/44 , (not FAK Y397 ) in C2C12 more than in endothelial cells and more than did angiopoietin-2 or cell matrices. EDTA, RGD-based peptides, and some integrin antibodies blocked these responses. Angiopoietin-1 activated HSM and NCM Akt S473 and MAPK p42/44 survival pathways. We propose that this novel function contributes to developmental and cardioprotective actions of angiopoietin-1 presently attributed to vascular effects alone. Angiopoietin-1 may prove therapeutically valuable in cardiac remodeling by supporting myocyte viability and preserving pump function. The full text of this article is available online at http://circres.ahajournals.org. (Circ Res. 2005;96:e8-e24.)Key Words: angiopoietin-1 Ⅲ angiopoietin-2 Ⅲ cardiac myocytes Ⅲ adhesion molecules Ⅲ myocyte apoptosis Ⅲ skeletal myocytes T here is growing consensus that cardiomyocyte (CM) apoptosis contributes to many cardiac diseases (eg, ischemia, 1 infarction, 2 hypertension, 3 myocarditis, 4 transplant rejection, 5 and heart failure 6,7 ). Research efforts are directed at defining the incidence of CM death, the contributions to cardiac dysfunction, and the consequences of inhibiting apoptosis. Incentive is based on the rationale that CM loss reduces contractile mass of the heart and may be a preventable catalyst of heart failure. In support of this concept, low levels of CM apoptosis (23 CM/10 5 nuclei) cause lethal cardiomyopathy in mice. 8 CM apoptosis rates are higher in cardiomyopathy patients (80 to 250 CM/10 5 nuclei) compared with healthy hearts (1 to 10 CM/10 5 nuclei). 9,10 Further, ischemic preconditioning upregulates bcl-2, a cytoprotective protein, and is linked to reduced apop...

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“…13,14 This decrease in ␤ 1 integrin expression is also noted in aging mouse myocardium. 6 We found that both RGD and blocking antibodies partially reduced infectivity, implicating the ␤ 1 integrin-RGD interaction as one of the mechanisms involved in the adenoviral infection process in cardiomyocytes in vitro.…”

Section: Discussionmentioning

confidence: 60%

“…12 ␤ 1 integrins are the prime isoform expressed in postnatal cardiac cells, 13 and ␣ 5 is not detected in adult rat cardiac myocytes. 14 To further explore the role of these integrins and determine the mechanism of decreased infectivity seen in aging cardiac myocytes, we (1) tested the efficiency of adenoviruses at mediating gene transfer and expression in aging cardiac myocytes in vitro, (2) extended these observations to another rat model of aging, (3) compared the level of adenovirus receptors and integrin expression (both CAR-dependent and -independent pathways) in aging versus control adult cardiomyocytes, and (4) studied the involvement of integrins in the mechanism of adenovirus infection in cardiomyocytes.…”

mentioning

confidence: 99%

Decreased Efficiency of Adenovirus-Mediated Gene Transfer in Aging Cardiomyocytes

et al. 2003

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Background-Aging is an independent risk factor for the development of cardiovascular disease. Clinical application of myocardial gene transfer may be best suited in the elderly. In vivo gene transfer by adenovirus is less efficient in aging myocardium. Methods and Results-When infected with adenovirus containing ␤-galactosidase (␤-gal) and green fluorescent protein (GFP) driven by cytomegalovirus promoters in vitro, aging rat cardiac myocytes exhibit significantly lower infectivity and delayed transgene expression compared with adult controls. Abnormalities of viral internalization may be one mechanism accounting for this difference. To investigate this, we studied expression levels of the coxsackievirus and adenovirus receptor (CAR) as well as other potential integrins involved in the internalization of adenoviruses. CAR expression tended to be upregulated whereas among potential integrins, ␣ 3 ␤ 1 was downregulated in aging cardiac myocytes. Blocking the ␤ 1 component of ␣ 3 ␤ 1 further decreased infectivity, suggesting that the interaction between the penton base of the adenovirus and ␤ 1 maybe a crucial component of the viral entry mechanism. Conclusions-These results suggest that it is integrin-stimulated internalization rather than the adenovirus-CAR interaction that plays a vital role in adenoviral entry. The downregulation of integrins observed in senescent cells may be a key mechanism accounting for the decrease in viral infectivity seen in these cells. These findings have implications for the gene therapy treatment of myocardial failure in the elderly.

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Expression of α and β integrins during terminal differentiation of cardiomyocytes

Abstract: These results suggest that progression through the cardiomyocyte cell cycle may be dependent upon cell attachment via integrin beta1 and correlate with changes that occur in beta1 spliced variants and their respective alpha isoforms.

Cited by 65 publications

References 44 publications

VEGF165 and angiopoietin-1 decreased myocardium infarct size through phosphatidylinositol-3 kinase and Bcl-2 pathways

VEGF165 and angiopoietin-1 decreased myocardium infarct size through phosphatidylinositol-3 kinase and Bcl-2 pathways

Angiopoietin-1 Promotes Cardiac and Skeletal Myocyte Survival Through Integrins

Decreased Efficiency of Adenovirus-Mediated Gene Transfer in Aging Cardiomyocytes

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