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Query: UNIPROT:P06889 (Mol)
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Scanning electron microscopy and transmission electron microscopy were used together with tannic acid and ruthenium-red staining to examine connective tissue damage caused by acute myocardial ischemia for 20, 40 and 120 min in pig hearts. The microsphere blood flow technique revealed that blood flow was approximately 0.02 ml/min/g in inner, middle and outer thirds of the ischemic zone. After 20 min of occlusion of the left anterior descending coronary artery, the collagen network and microfilaments became irregularly arranged. After 40 min of occlusion, ruthenium-red positive glycoprotein material around the collagen fibrils and elastin began to disappear. After 2 h occlusion, the collagen fibrils and microfilaments had separated from the basement membrane. Collagen fibrils, elastic fibers, and microfilaments were broken down and were found in decreased quantities. These results have revealed that the connective tissue remains intact during the first 20 min of coronary occlusion despite zero blood flow and mild cellular changes but does undergo prominent alterations after 40 min of occlusion.
J Mol Cell Cardiol 1983 Apr
PMID:Connective tissue changes in early ischemia of porcine myocardium: an ultrastructural study. 687 83

In porcine heart, embolization of small coronary arteries with microspheres in 25 microns in diameter induces collateral capillary vessel growth by angiogenesis in and around focal necrosis. By histological analysis the inflammatory infiltrates in this porcine tissue were characterized by numerous monocytes/macrophages and fibroblasts as well as neutrophils and numerous capillaries, some in mitosis. The aim of the present study, therefore, was to clarify the role of monocytes/macrophages and fibroblasts in angiogenesis and in repair in ischemic porcine myocardium. Using a human acidic fibroblast growth factor (aFGF) cDNA probe for in situ hybridisation labeling for aFGF mRNA was seen in monocytes and macrophages only, beginning at day 1, with a maximum at 3 and 7 days, and minimal labeling at 4 weeks. We have also shown, with a specific antibody and fluorescence microscopy, that tumur necrosis factor alpha (TNF alpha) follows the same time sequence and that it is produced by monocytes/macrophages. The number of capillaries in infiltrates at 3 and 7 days as revealed by the lectin Dolichus Biflorus Agglutinin was high and declined at 4 weeks. In situ hybridisation using a rat cDNA probe for fibronectin showed the increased production of fibronectin mRNA in fibroblasts. To describe the expression of fibronectin and the collagens I, III, VI immunohistochemistry was used. A comparison showed that fibroblasts produced fibronectin mRNA starting at day 3, but the protein was only maximally expressed at day 7 and 4 weeks. Collagen I, III, VI expression was highest at 1-4 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Biochem
PMID:Importance of monocytes/macrophages and fibroblasts for healing of micronecroses in porcine myocardium. 749 42

Protein distribution and mRNA expression of basement membrane collagen (type IV) during follicle formation were studied using serial sections from 24, 48 and 72 hrs. old rat ovaries. Collagen type IV, a protein found only in the basal lamina of the basement membrane, was localized under light microscope using a polyclonal antibody. During the first 24 hrs. postpartum, immunostaining was found as thin septa separating the clusters from the stroma. By 72 hrs. postpartum, immunostaining was found around each newly formed primordial follicle. The cell types involved in collagen type IV synthesis were determined by in situ hybridization using a biotinylated riboprobe. Before the follicles had been formed, the stromal cells showed intense staining while the epithelial presumptive granulosa cells showed a pale staining. However, after a follicle had been formed, some of the granulosa cells enclosed within the follicular basement membrane showed strong staining for the message. The presumptive granulosa cells are presumed to be the progenitors of granulosa cells. If so, these observations suggest that the expression of the message coding for collagen type IV by the granulosa cells may be a marker for commitment of the undifferentiated cell to the granulosa cell lineage.
Cell Mol Biol (Noisy-le-grand) 1994 Sep
PMID:Protein distribution and gene expression of collagen type IV in the neonatal rat ovary during follicle formation. 781 84

Collagen addition to platelets suspended in Calcium-free medium induces slow shape change followed by fast aggregates formation. Time courses of membrane phospholipids metabolism and arachidonic acid oxidative metabolism indicate that phospholipase C is the immediate target of the stimulus, and subsequently phospholipase A-2 is activated by synergistic action of released calcium and protein kinase C.
Biochem Mol Biol Int 1994 Oct
PMID:Phospholipids metabolism in platelets stimulated with collagen. 786 94

Collagen fibrils are among the most abundant protein polymers in living organisms. While the longitudinal packing of molecules in the fibrils has been agreed on for many years, there is continuous disagreement over the lateral packing. In this work, we describe a set of computer graphics programs that can be used to visualize fibril packing and simulate fibril growth. An example of a model and simulation are presented.
J Mol Graph 1994 Jun
PMID:Visualizing collagen fibril growth. 791 52

Myocardial fibrosis is associated with an activated renin-angiotensin-aldosterone system (RAAS). In renovascular hypertension, this presents as a reactive perivascular and interstitial fibrosis in not only the pressure overloaded, hypertrophied left ventricle but also the normotensive, nonhypertrophied right ventricle. It therefore would appear that circulating hormonal and not hemodynamic factors are responsible for this adverse fibrous tissue response. To ascertain whether the RAAS effector hormones angiotensin II (AII) or aldosterone (ALDO) directly stimulate collagen synthesis or inhibit collagenase production we used cell culture. Adult rat cardiac fibroblasts (Fb) were cultured since these cells express mRNA for types I and III collagens, the major fibrillar collagens in the heart, and collagenase or matrix metalloproteinase 1 (MMP 1), the key enzyme for interstitial collagen degradation. Collagen synthesis, determined by 3H-proline incorporation, and collagenase activity were measured in confluent, quiescent Fb after 24 h incubation with various concentrations of AII or ALDO (10(-11)-10(-6)M) in the presence or absence of either 10(-5)M type 1 (DuP 753) and type 2 (PD 123177) AII or 10(-9)-3 x 10(-6)M ALDO (spironolactone) receptor antagonists, respectively. Collagen synthesis, normalized per total protein synthesis, increased significantly (P < 0.005) after incubation with either 10(-9)M ALDO (5.9 +/- 1.0%) or 10(-7)M AII (5.3 +/- 1.2%) compared with untreated control cells (2.9 +/- 0.5%) of the same passage (p6-p10). This increase in collagen synthesis could be completely abolished by either types 1 or 2 AII receptor antagonists in AII stimulated Fb or the competitive ALDO receptor antagonist, spironolactone, at equimolar concentration in ALDO stimulated Fb. AII significantly decreased collagenase activity which could be completely abolished by PD 123177, but not DuP 753, while ALDO had no effect on collagenase activity. The mineralocorticoid, ALDO, stimulates collagen synthesis in cultured adult rat cardiac Fb in concentrations similar to those found in plasma in renovascular hypertension and this response appears to occur via type I corticoid receptors. AII appears to stimulate collagen synthesis by both type 1 and 2 AII receptors, but only in high concentrations that could be generated locally within the myocardium. In addition, AII unlike ALDO inhibits collagenase activity that could be attenuated only by type 2 receptor blockade. These findings suggest a direct interaction between ALDO, AII and cardiac Fb in mediating myocardial fibrosis in hypertensive heart disease.
J Mol Cell Cardiol 1994 Jul
PMID:Collagen metabolism in cultured adult rat cardiac fibroblasts: response to angiotensin II and aldosterone. 796 49

Sex-related differences in predisposition to heart diseases have long been recognized. The molecular and cellular bases for this difference are unknown. In this study we have compared expression of genes for various structural and functional proteins of muscle and interstitial compartments of the myocardium in the adult and neonatal, male and female rat heart. We have also compared cultured cardiac fibroblasts from male and female hearts with regards to gene expression and proliferative capacity. We showed that in the adult rats, the abundance of mRNAs for contractile proteins alpha- and beta-myosin heavy chain (MHC) is higher in the heart of female rats than in that of age-matched male rats. However, the difference in mRNA level for alpha-MHC was more drastic (736%, P < 0.001) than that for beta-MHC (469%, P < 0.001). mRNA levels for sarcomeric actin in the female heart were greater by 79% (P < 0.001). Collagen type I had a significantly higher (303%, P < 0.01) mRNA level in the female heart compared with the male heart. mRNAs for TGF-beta 1, cytoskeletal actin and connexin 43 were also higher (150%, P < 0.01; 130%, P < 0.01, and 150%, P < 0.01, respectively) in the female heart compared with age-matched male heart. There were no significant sex-related differences at the mRNA levels for the above proteins in ventricular tissue from neonatal male and female littermates. At the cellular level, cardiac fibroblasts obtained from adult and neonatal hearts of both sexes were comparable with respect to the abundance of mRNAs for collagen type I, TGF-beta 1 or cytoskeletal actin. However, DNA synthesis, as measured by [3H]thymidine incorporation, was higher (328%, P < 0.01) in cells from adult female heart compared with that in cells from adult male rat heart. This difference was even more pronounced in cardiac fibroblasts obtained from newborn female rats (933%, P < 0.001) compared with that in cells obtained from newborn male rat hearts. Together, these findings show that there are sex-related differences in gene expression for most major proteins in heart tissue and that this phenomenon is associated with the post-pubertal period. These findings further suggest that sex-related differential gene expression and DNA synthesis in cardiac cells are due to the regulatory effects of male- and female-specific hormones.
J Mol Cell Cardiol 1994 Feb
PMID:Gender-specific differences in expression of mRNAs for functional and structural proteins in rat ventricular myocardium. 800 87

A collagen network, composed largely of type I and III fibrillar collagens, is found in the extracellular space of the myocardium. This network has multiple functions which includes a preservation of tissue architecture and chamber geometry. Given its tensile strength, collagen is a major determinant of tissue stiffness. Its disproportionate accumulation, in the form of either a reactive or a reparative fibrosis, further increases stiffness. A degradation of collagen tethers, on the other hand, is an anatomic requisite for a distortion in tissue architecture and a reduction in stiffness that can lead to chamber dilatation, wall thinning, and even rupture of the myocardium. Collagen turnover in the myocardium is dynamic. When synthesis exceeds degradation, an adverse accumulation of collagen appears to distort tissue structure. This is true for either the hypertrophied and/or nonhypertrophied ventricle. Factors that contribute to the appearance of myocardial fibrosis are largely different from those that promote cardiac myocyte growth. Included amongst these fibrogenic factors are effector hormones of the reinin-angiotensin-aldosterone system (RAAS). Studies conducted both in intact animals (relative to dietary sodium intake) and in cultured adult cardiac fibroblasts have pointed toward the association between collagen accumulation and chronic elevations in circulating angiotensin II and aldosterone. A tissue hormonal system involving angiotensin II, endothelins and bradykinin, may likewise regulate fibrogenesis. In this regard, angiotensin converting enzyme is found in connective tissue of the normal heart, including the matrix of heart valves and the adventitia of the intramural coronary arteries, and fibrous tissue that forms following infarction or with chronic RAAS activation. The importance of ACE in the regulation of local angiotensin II and bradykinin levels and their contribution to collagen turnover is a fruitful area of research with important clinical implications. The myocardium also contains a proteolytic system, including collagenase. The characteristics and regulation of matrix metalloproteinases and their tissue inhibitors in various cardiovascular disease states requires further investigation.
J Mol Cell Cardiol 1994 Mar
PMID:Collagen network of the myocardium: function, structural remodeling and regulatory mechanisms. 802 11

The tight-skin (Tsk) mouse is a genetic model of pulmonary emphysema. In this mouse, right ventricular hypertrophy (RVH) starts to develop at approximately 8 months of age, probably as a consequence of the emphysema. The aim of the present study was to investigate cardiac collagen synthesis, content, and types both before and during the development of RVH. Collagen synthesis, assessed by the [3H]proline incorporation method, was significantly increased in the right ventricle of 3-month-old Tsk mice. This was accompanied by a marked increase in right ventricle collagen content. Collagen typing showed no difference from controls. At 8 months of age collagen synthesis had returned to control values, right ventricular collagen content was elevated but held lower values than at 3 months, and collagen typing showed a prevalence of the more compliant type III. By 16 months of age, right ventricular collagen content had returned to control values and there was a shift in collagen types due to a relative increase of the more rigid type I. At 24 months of age right ventricular collagen content was increased again and collagen type I continued to predominate. These results suggest a dynamic role for collagen both before and during the development of RVH secondary to emphysema.
Exp Mol Pathol 1994 Apr
PMID:Cardiac collagen changes during the development of right ventricular hypertrophy in tight-skin mice with emphysema. 807 May 38

The possibility that extracellular matrix-cell surface interaction might lead to signalling was examined in human mononuclear cells. In mononuclear cells loaded with Indo-1 acetoxymethylester, collagen binding elicited a 2-3 fold increase in cytosolic free calcium concentration within seconds. Plasma fibronectin, serum albumin and heparin did not cause any significant change in intracellular calcium levels. Collagen I, collagen IV and glucosylated collagen I evoked an increase in intracellular Ca++ both in the presence and absence of extracellular calcium. However, in the presence of 2mM EDTA, the increase in cytosolic free calcium concentration caused by collagen I and collagen IV was partly abolished, suggesting the requirement of a cation-dependent interaction of collagen with mononuclear cells. Glucosylated collagen induced intracellular calcium mobilization even in the presence of EDTA suggesting a cation-independent interaction. These results indicate that collagen binding induces rapid mobilization of calcium in human mononuclear cells, apparently from intracellular sources.
Biochem Mol Biol Int 1993 Dec
PMID:Binding of collagen causes intracellular mobilization of calcium in human mononuclear cells. 813 1


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