Fibronectin Penetration into Heart Myocytes Subjected to Experimental Ischemia by Coronary Artery Ligation
Department of Anatomy and Cell Biology, University of Bergen, Norway. Acta Anatomica
02/1995; 152(2):119-26. DOI: 10.1159/000147690
Using confocal microscopy and immunocytochemistry we have studied early changes in distribution of fibronectin (FN) in myocardial cells of rats subjected to experimental acute myocardial ischemia (AMI) by coronary ligation for several periods of 0.5 h to 6 days. In sham-operated and nonoperated rats, FN was present in the interstitium around the myocytes, and in their transverse tubules (TT). Already after 0.5 h of ischemia there was a well-defined increase of immunoreactive FN in focal areas of the interstitium of the hypoperfused portion, and distinct penetration into adjacent myocytes. The early penetration of FN into myocytes appears to follow a path through the TT, with a codistribution with actin in the I bands. This process precedes a total and diffuse infiltration of FN into the cytoplasm of disintegrating myocytes at later stages of coronary occlusion.
Available from: Behrouz Zandieh Doulabi
- "Two extracellular matrix (ECM) molecules of human mesenchymal stem cells are important for stem cell survival and differentiation towards other lineages: laminin and fibronectin (Hashimoto et al. 2006; Salasznyk et al. 2004; Wijelath et al. 2004). Both these proteins are expressed in the normal heart and increase after MI (Froen and Larsen 1995; Knowlton et al. 1992; Willems et al. 1996). In vivo, an effect of these ECM molecules on stem cell survival and differentiation can be expected if stem cell therapy is applied once these proteins have accumulated. "
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ABSTRACT: Adipose-derived stem cells (ASCs) are promising candidates for therapy in myocardial infarction (MI). However, the frequency of human ASCs that differentiate towards cardiomyocytes is low. We hypothesized that adherence to extracellular matrix molecules that are upregulated after MI might increase human stem cell differentiation towards cardiomyocytes. We analysed putative ASC differentiation on fibronectin-coated, laminin-coated and uncoated culture plates. Expression of cardiac markers in cells was analysed 1, 3 and 5 weeks after stimulation with 5-aza-2-deoxycytidine. After 1 week, mRNA expression of myosin light chain-2alpha (MLC-2alpha), an early marker in cardiomyocyte development, was increased significantly in treated cells, independent of coating. At 5 weeks, however, mRNA expression of the late cardiomyocyte development marker SERCA2alpha was only significantly increased in 5-aza-2-deoxycytidine-treated cells cultured on laminin. Significantly higher numbers of cells were immunopositive for MLC-2alpha in cultures of treated cells grown on laminin-coated wells, when compared with cultures of treated cells grown on uncoated wells, both at 1 week and at 5 weeks. Furthermore, after 3 weeks, significantly more alpha-actinin- and desmin-positive cells were detected after treatment with 5-aza-2-deoxycytidine, but only in uncoated wells. After 5 weeks, however, the number of desmin-positive cells was only significantly increased after treatment of cells with 5-aza-2-deoxycytidine and culture on laminin (61% positive cells). Thus, we have found that a high percentage of human ASCs can be differentiated towards cardiomyocytes; this effect can be improved by laminin, especially during late differentiation.
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ABSTRACT: Previous work has shown that neutrophils isolated from whole blood adhere to cardiac-myocytes via CD18 (beta 2 integrin) to cause injury to the heart cells. In vitro, we have found that upon endothelial transmigration, neutrophils can also express alpha 4 beta 1; however, whether this contributes to neutrophil adhesion to parenchymal cells remains entirely unknown. Unstimulated and tumor necrosis factor-alpha-stimulated rat cardiac myocytes adherent to gelatin-coated coverslips supported N-formyl-Met-Leu-Phe (fMLP)-induced neutrophil (isolated from whole blood) adhesion entirely via CD18 (blocked with monoclonal antibody [mAb] WT-3). Emigrated neutrophils spontaneously adhered to cardiac myocytes also entirely via CD18. However, if fMLP was used to restimulate emigrated neutrophils, the adhesion to cardiac myocytes was entirely independent of CD18. Although an anti-alpha 4 integrin antibody (mAb TA-2) alone did not reduce the emigrated neutrophil-myocyte interaction, dual administration of TA-2 and WT-3 reduced adhesion by 81%. alpha 4 integrin was expressed in small amounts on the surface of circulating neutrophils, increased following transmigration, and then increased > 5-fold after restimulation of these emigrated neutrophils. In the presence of the anti-CD18 antibody, a fibronectin fragment (FN-40) but not a vascular cell adhesion molecule-1 antibody (mAb 5F10) inhibitied neutrophil-myocyte interactions by 80%. Similar results were seen when the rat chemokine CINC-gro was used instead of fMLP, suggesting that the alpha 4-dependent adhesion was not specific to fMLP. These data demonstrate that alpha 4 integrin can be physiologically induced to increase in number and avidity after neutrophil emigration and that this adhesion molecule can cause firm adhesion to fibronectin on parenchymal cells, including rat cardiac myocytes.
Available from: Martin Witt
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ABSTRACT: The aim of this work was to study the effect of a dose of 150 microCi 131I on the barrier properties of the thyroid epithelium in pregnant female rats. Thirty-five female Wistar rats were divided into a control and four experimental groups (each distinguished by the time of 131I injection: group I--no less then 12 days before mating; groups II, III, and IV--on 5th, 10th, and 16th days of gestation, respectively). The thyroid glands were fixed in Bouin's fluid, embedded in paraffin, and stained immunohistochemically for thyroglobulin and fibronectin. In group IV the appearance of follicles with fibronectin-positive colloid demonstrates the penetration of blood plasma into the follicular lumen. There are more fibronectin positive follicles in group III. Regardless of the nature of the follicles' contents, numerous thyrocytes with an intensive fibronectin positive reaction begin to appear in the follicles. In group II the number of fibronectin positive follicles and thyrocytes is clearly reduced, and in group I only a few remain. In group IV there is a noticeable reduction in the quantity of colloid inside the follicles and often an absence of any thyroglobulin positive reaction. There are thyrocytes in which thyroglobulin positive granules localized in the basal zone. There is thyroglobulin positive staining in the stroma and blood vessels. In group II thyroglobulin is no longer found in the stroma. Small doses of 131I provoke a serious breakdown in the thyroid epithelium's barrier properties, although these changes are of a transient nature. The central zone of the thyroid gland reacts more actively and dynamically to exposure to radioactive iodine than the peripheral zone.
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