Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 8 de 8
Filter
Add more filters










Database
Language
Publication year range
1.
Exp Cell Res ; 227(1): 135-45, 1996 Aug 25.
Article in English | MEDLINE | ID: mdl-8806460

ABSTRACT

Developmental studies have demonstrated that the vascular smooth muscle cells (VSMC) present within the elastic arteries are differentiated from two definitive origins, the neural crest and the mesoderm. Cells from these distinct progenitors differ in their ability to determine long-range spatial order of the extracellular matrix, in proliferative responses, and in the expression of critical proteins. The present study utilizes collagen gel contraction assays and the analysis of integrin receptor subunit expression to evaluate cell-matrix interactions. In the presence of serum and transforming growth factor-beta 1 (TGF) or TGF-beta 1 alone, VSMC isolated from the abdominal aorta (AA-VSMC) were found to contract collagen matrices to a significantly greater extent than VSMC from the thoracic aorta (TA-VSMC). However, in TA-VSMC, beta 1 integrin and gel contraction were stimulated only in the presence of serum factors. Metabolic labeling and immunoprecipitation of integrin subunits revealed that TGF-beta 1 induced beta 1 and alpha 5 integrin subunits in AA-VSMC four-and ninefold, respectively. AA-VSMC gel contraction stimulated by serum and TGF-beta 1 alone was inhibited with anti-beta 1 integrin antibody by 70 and 100%, respectively. However, the beta 1 integrin-specific antibody inhibited serum-induced TA-VSMC gel contraction by 25%. The data suggest that vascular smooth muscle cell ontogeny is an important determinant of cell function, phenotype, and response to growth factors such as TGF-beta 1.


Subject(s)
Antigens, CD/genetics , Collagen/pharmacology , Extracellular Matrix/physiology , Integrin beta1/genetics , Muscle, Smooth, Vascular/embryology , Animals , Aorta, Abdominal , Aorta, Thoracic , Base Sequence , Blood , Cell Division , Chick Embryo , Gels , Gene Expression/physiology , Integrin alpha5 , Molecular Sequence Data , Muscle, Smooth, Vascular/cytology , Muscle, Smooth, Vascular/physiology , Neural Crest/cytology , RNA, Messenger/analysis , Transforming Growth Factor beta/pharmacology
2.
Am J Pathol ; 147(2): 461-75, 1995 Aug.
Article in English | MEDLINE | ID: mdl-7639338

ABSTRACT

In heart transplantation, long-term engraftment success is severely limited by the rapid development of obliterative disease of the coronary arteries. Data from various groups have been suggestive of a pathogenetic role of herpesviruses, particularly human cytomegalovirus, in accelerated allograft coronary artery disease; however, results are not yet conclusive. This study examines the hypothesis that human cytomegalovirus infection of allograft tissues is related pathogenetically and directly to accelerated coronary artery disease. Using in situ DNA hybridization and polymerase chain reaction, we examined particular coronary artery segments from 41 human heart allografts (ranging from 4 days to greater than 4 years after transplantation; mean, 457 days) and 22 donor age- and gender-comparable, coronary site-matched trauma victims for presence of human cytomegalovirus DNA. Human cytomegalovirus genome was detected in 8 of 41 (19.5%) allografts and in 1 of 22 (4.5%) control hearts. This difference in positivity was not statistically significant (P = 0.10). In the human cytomegalovirus-positive hearts, viral genome was localized to perivascular myocardium or coronary artery media or adventitia. Human cytomegalovirus genome was not detected in arterial intima of any allograft or control heart, although human cytomegalovirus genome was readily identified within intima of small pulmonary arteries from lung tissue with human cytomegalovirus pneumonitis. By statistical analyses, the presence of human cytomegalovirus genome was not associated with the nature or digitized extent of transplant arteriopathy, evidence of rejection, allograft recipient or donor serological data suggestive of human cytomegalovirus infection, duration of allograft implantation, or causes of death or retransplantation. Thus, our data indicate a low frequency of detectable human cytomegalovirus genome in accelerated coronary artery disease and do not support a direct role for human cytomegalovirus in vascular wall infection or in the development of accelerated coronary artery disease.


Subject(s)
Coronary Disease/genetics , Cytomegalovirus/genetics , Genome, Viral , Heart Transplantation , Adolescent , Adult , Aged , Base Sequence , Coronary Vessels/immunology , Coronary Vessels/pathology , Female , Gene Frequency , Humans , In Situ Hybridization , Male , Middle Aged , Molecular Probes/genetics , Molecular Sequence Data , Polymerase Chain Reaction , Transplantation, Homologous
3.
Matrix Biol ; 14(7): 573-82, 1995 Jul.
Article in English | MEDLINE | ID: mdl-8535607

ABSTRACT

The elastic matrix of the large arteries shows a high level of spatial order. However, the mechanisms by which such order is established and maintained are largely unknown. The embryonic development of the avian heart and great vessels provides an appropriate model to investigate these mechanisms. In control embryos, an elastic matrix with a high level of spatial order develops in the nascent great vessels. But after the normal vascular smooth muscle (VSM) progenitor cells in the great vessels are experimentally replaced by other VSM progenitor cells, the elastic extracellular matrix is congenitally disordered. The present study used this model to test the hypothesis that the proteoglycan decorin was involved in the establishment and maintenance of the normal three-dimensional spatial order of the vascular elastic matrix. The temporospatial expression of decorin was analysed during development of normal vessels and in experimental vessels with surrogate VSM. The results showed the following: (1) the expression of decorin was related in time and space to the establishment of large helical collagen type III fibers that are characteristic of the normal elastic extracellular matrix; (2) in the experimental extracellular matrix there were few helical fibers of collagen type III, but those that were present remained positive for decorin; and (3) in both control and experimental vessels, decorin associated with neither fibers of collagen type I nor fibers of collagen type III in any conformation other than the large helical fibers. These data indicate a previously unrecognized relationship between decorin and the spatial order of the physiologically significant helical fibers of collagen type III.


Subject(s)
Aorta, Thoracic/embryology , Collagen/metabolism , Embryonic and Fetal Development , Extracellular Matrix/physiology , Proteoglycans/metabolism , Animals , Chick Embryo , Decorin , Elastic Tissue/embryology , Extracellular Matrix Proteins , Fluorescent Antibody Technique
4.
J Heart Lung Transplant ; 13(5): 824-33, 1994.
Article in English | MEDLINE | ID: mdl-7803423

ABSTRACT

Previous angiographic observations have characterized transplant atherosclerosis as a generally diffuse and more distally severe disease with obliteration of secondary branches. However, it has not been firmly established that the disease is structurally and biologically more severe distally. We evaluated this hypothesis with computer-based digitization of subserial segments of the entire perfusion-fixed left anterior descending coronary artery (100 mm Hg for 1 hour with 10% formaldehyde solution) in 25 allografts at autopsy or explant (19 male and 6 female patients; mean age = 50 years, range 16 to 66; mean implant duration = 490 days, range 3 to 1610). The area, thickness, circumference of the intima and media, and the relative and absolute luminal narrowing were evaluated in a mean of 10 left anterior descending coronary artery sections per allograft. The percentage of luminal narrowing (intimal area/[intimal area + luminal area] x 100) was similar between proximal and distal segments of the left anterior descending coronary artery (45% versus 41%, p > 0.05), and the mean absolute intimal thicknesses (in millimeters) of proximal and distal segments of the left anterior descending coronary artery also were not different (0.32 versus 0.22, p > 0.05). In addition, the 95% confidence intervals for intimal thicknesses of proximal and distal segments were comparable. Because the absolute arterial size of proximal segments is naturally larger than that of distal segments (external diameter 9.37 versus 6.79, p < 0.0001), an appearance of progressive tapering may be visualized angiographically, even though the biologic severity of the disease is geographically uniform. Similarly, observations of obliterated secondary branches in distal segments may result from naturally smaller distal luminal areas which may be occluded by less intimal thickening than would be required proximally. These data emphasize that transplant atherosclerosis is biologically uniform from proximal to distal locations. Etiologic and pathogenetic studies on proximal or distal segments should be equally informative.


Subject(s)
Coronary Artery Disease/pathology , Coronary Vessels/pathology , Heart Transplantation/pathology , Tunica Intima/pathology , Adolescent , Adult , Aged , Case-Control Studies , Coronary Angiography , Coronary Artery Disease/diagnostic imaging , Elastic Tissue/diagnostic imaging , Elastic Tissue/pathology , Female , Humans , Image Processing, Computer-Assisted , Male , Middle Aged , Signal Processing, Computer-Assisted , Software , Transplantation, Homologous , Tunica Intima/diagnostic imaging , Tunica Media/diagnostic imaging , Tunica Media/pathology
5.
Clin Transplant ; 8(3 Pt 2): 336-40, 1994 Jun.
Article in English | MEDLINE | ID: mdl-8061377

ABSTRACT

The degree to which transplant arteriopathy in solid organ allografts is an atheromatous process remains somewhat controversial. If atheromata develop as common and integral components of the arteriopathic lesions, then the process may be approached therapeutically in a manner analogous to native atheromatous diseases. Approaches to understanding the arteriopathic process may include not only the modulation of alloimmunity, but also the interruption of "storage" phenomena. We have examined the epicardial coronary arteries of nearly 50 explanted human heart allografts using biochemical, morphological, morphometrical, immunohistochemical, and molecular techniques in an effort to establish the degree, nature, and distribution of lipid accumulation in the vessel walls. Concomitantly, we studied the ascertainment of proteoglycan gene expression, represented by biglycan and decorin messenger RNA, and the localization of proteoglycan proteins in the vessels. The degree of lipid and proteoglycan buildup in both the intima and media of transplanted vessels is striking, and correlated strongly with intimal thickening, cross-sectional area reduction of the lumen, cumulative cyclosporine dose, corticosteroid dose, and serum cholesterol levels. Notably, lipid accumulation is not related to implant duration, this being true in an unselected series of "failed" allografts ranging from 4 to 1610 days post-transplant. The profound lipid accumulation in coronary walls of many grafts begins very early post-transplant and appears to contribute substantially to intimal thickening. Whether dysregulation of proteoglycan production leads to entrapment of lipids and lipoproteins remains an important and testable hypothesis.


Subject(s)
Coronary Artery Disease/metabolism , Graft Rejection/metabolism , Heart Transplantation/physiology , Lipid Metabolism , Proteoglycans/metabolism , Chronic Disease , Coronary Artery Disease/microbiology , Coronary Artery Disease/pathology , Coronary Vessels/metabolism , Coronary Vessels/microbiology , Coronary Vessels/pathology , Cytomegalovirus/isolation & purification , Elastic Tissue/metabolism , Elastic Tissue/pathology , Gene Expression , Graft Rejection/microbiology , Graft Rejection/pathology , Heart Transplantation/pathology , Humans , Proteoglycans/genetics , Risk Factors
6.
J Heart Lung Transplant ; 11(3 Pt 2): S14-20, 1992.
Article in English | MEDLINE | ID: mdl-1320406

ABSTRACT

In conclusion, a great deal of indirect and inferential data point to herpesviruses as having a role in atherogenesis. It has been shown that the herpesviruses are able to remain within vascular tissue in a latent state, allowing for reactivation to occur with subsequent sequelae of an active infection. Herpesviruses affect the cellular metabolic activity of cells, induce the accumulation of lipids, and inhibit the production of matrix proteins. They have the ability to inhibit endothelial cell binding to the basement membrane. It is also known that the herpesviruses, particularly CMV, can initiate a variety of immunologic responses that may contribute to endothelial damage, precipitating atherogenesis. We are only beginning to understand how CMV may participate in ACAD. Greater attention must be focused on the exact cause-and-effect relationship between CMV infection and ACAD. Even the presence of CMV genomes in arterial walls of allografts must be viewed conservatively in the knowledge of CMV ubiquity and other probable contributions to ACAD. If CMV is involved in the development of ACAD, as an active or latent infection, directly or indirectly, it probably involves numerous coexistent mechanisms (Figure 5).


Subject(s)
Coronary Artery Disease/etiology , Cytomegalovirus Infections/complications , Endothelium, Vascular , Heart Transplantation , Herpesviridae/pathogenicity , Postoperative Complications , Cytomegalovirus Infections/immunology , Herpesviridae/immunology , Herpesviridae/metabolism , Humans , Lipid Metabolism , Microscopy, Electron , Transplantation, Homologous
7.
Atherosclerosis ; 83(2-3): 137-46, 1990 Aug.
Article in English | MEDLINE | ID: mdl-1978683

ABSTRACT

Despite great interest in the role of lipids in overall and disease-free survival, virtually no information is available on the lipids, lipoproteins and apolipoproteins of persons over 90 years of age. Furthermore, the genetic underpinnings of atherosclerosis and the particular genetic factors responsible for protection against coronary artery disease remain speculative. In Bloomfield, Nebraska, we studied 41 nonagenarians (10 males, 31 females), with a mean age of 92.7 years, in whom lipids, lipoproteins, apolipoproteins and restriction fragment length polymorphisms (RFLPs) of genes for apolipoprotein B (apo B), aop AI and apo CIII were assessed. Nearly complete historical, physical and laboratory data were obtained on 39 subjects. The mean diastolic and systolic blood pressures for this group were nonhypertensive, body mass indices (weight/height2) had a mean of 23.9 and triceps skinfold thickness measurements an overall mean of 14.8 mm. The mean total serum cholesterol was 5.42 mmol/l. HDL-cholesterol levels in females persisted to be higher when compared to males (P less than 0.013). The allele frequencies for apo AI (MspI and PstI), apo CIII (Sst) and apo B (XbaI) gene RFLPs were typical for larger population studies. In these preliminary studies, we did not identify a distinctive phenotype, genotype, or phenotype-genotype relationship. Diversity of cardiovascular risk was the hallmark of these nonagenarians.


Subject(s)
Apolipoproteins/genetics , Coronary Artery Disease/genetics , Genotype , Lipids/genetics , Lipoproteins/genetics , Phenotype , Aged , Aged, 80 and over , Body Mass Index , Cholesterol, HDL/genetics , Cholesterol, LDL/genetics , DNA Probes , Dietary Fats/administration & dosage , Energy Intake/physiology , Female , Geriatric Assessment , Humans , Longevity/genetics , Male , Polymorphism, Restriction Fragment Length , Risk Factors , Sex Factors
SELECTION OF CITATIONS
SEARCH DETAIL
...