Transforming growth factor-ß1 SMAD effectors and medial cell number in ascending aorta diseases.

In ascending aorta aneurysms and dissections, the extracellular matrix is degraded. Transforming growth factor (TGF)-ß1 modulates its synthesis. The production and presence of SMADs, intracellular effectors of TGF-ß1 signaling, were analyzed in patients with these diseases. To verify whether medial cells are lost, their total numbers were computed. Ascending aorta samples from 19 patients and 18 controls underwent immunoperoxidase reactions to SMADs 2, 3, 4, and 7. Positive and negative cells were counted, and total numbers of cells and positive/total ratios were calculated. Samples from other 14 patients and 7 normal controls were used for the quantification of SMAD3, SMAD4, and SMAD7 mRNA. For SMAD4, both mRNA (2.36 vs. 0.37, P=.03) and ratio of positive cells (0.94 vs. 0.73, P=.02) are increased in patients with ascending aortic diseases. SMAD3 mRNA was also increased (1.19 vs. 0.20, P=.05). The cell ratios of this and the other SMADs, SMAD7 mRNA, and the total cell count did not differ between groups. In conclusion, in ascending aortic aneurysms and dissections, there is an increase in SMAD4, implicated in extracellular matrix production, possibly as an attempt to compensate for extracellular matrix deficiency. Lost medial cells are replaced, since their number is not diminished.

Why do aortas cleave or dilate? Clues from an electronic scanning microscopy study in human ascending aortas.

In ascending aorta aneurysms (AscAA) the whole vessel wall dilates, while in aortic dissections (AD) the wall cleaves into two sheets. Both may present fine elastic fragmentation and a decrease in collagen. We analyzed whether alterations in the three-dimensional structure of these fibers could be involved in the pathogenesis of AscAA/AD. Specimens obtained at surgery for these diseases (n = 4 for each) and on coronary artery bypass surgery (controls, n = 4) were submitted to treatments which either preserve collagen or the elastic structure. These samples were examined by scanning electron microscopy. In all groups most of the collagen fibers were packed, forming laminar structures very similar to the elastic lamellae. In AscAA/AD, the fibers showed signs of degradation and/or fragmentation. Elastic tissue was distributed in large sheets with fenestrations, with smaller branches between them. In 1 of the dissection cases and 2 of the aneurysm cases elastic sheet fragmentation, which under light microscopy seems to be located at random, had a pattern of clefts which were irregular but approximately transversal to the main axis of the wall. The recognition of this pattern and the degradation/fragmentation of collagen and elastic fibrils facilitates understanding of why the wall is weak and affected by aneurysms and dissections.

In situ delivery of bone marrow cells and mesenchymal stem cells improves cardiovascular function in hypertensive rats submitted to myocardial infarction.

This work aimed to evaluate cardiac morphology/function and histological changes induced by bone marrow cells (BMCs) and cultured mesenchymal stem cells (MSCs) injected at the myocardium of spontaneously hypertensive rats (SHR) submitted to surgical coronary occlusion. Female syngeneic adult SHR, submitted (MI) or not (C) to coronary occlusion, were treated 24 h later with in situ injections of normal medium (NM), or with MSCs (MSC) or BMCs (BM) from male rats. The animals were evaluated after 1 and 30 days by echocardiography, histology of heart sections and PCR for the Y chromosome. Improved ejection fraction and reduced left ventricle infarcted area were observed in MSC rats as compared to the other experimental groups. Treated groups had significantly reduced lesion tissue score, increased capillary density and normal (not-atrophied) myocytes, as compared to NM and C groups. The survival rate was higher in C, NM and MSC groups as compared to MI and BM groups. In situ injection of both MSCs and BMCs resulted in improved cardiac morphology, in a more physiological model of myocardial infarction represented by surgical coronary occlusion of spontaneously hypertensive rats. Only treatment with MSCs, however, ameliorated left ventricle dysfunction, suggesting a positive role of these cells in heart remodeling in infarcted hypertensive subjects.

Picrosirius-polarization staining method as an efficient histopathological tool for collagenolysis detection in vesical prolapse lesions.

The Picrosirius-polarization method has been indicated as a selective histochemical stain for collagen detection in tissue sections. This method can also be of value for studying collagen degradation given that, under polarized light, collagen displays birefringence due to its molecular order. The aim of this study is to highlight this staining method as an additional instrument for a rapid and excellent confirmatory diagnosis of the presence of collagenolysis in connective tissue in the vaginal wall with vesical prolapse lesion, in tissue sections. Dramatic changes in collagen morphology were found in vaginal mucosa in vesical prolapse disorder: they were weakly stained by Sirius red and under polarized light appeared as thin, pale (weakly birefringent), greenish, and with fibers more scattered, while the histoarchitecture of the organ showed a disrupted appearance. Thus, in the present study, we showed in vaginal mucosa in the vesicle prolapse that corroded collagenous framework appears as fragmentary and irregularly separated collagenous structures, that are weakly birefringent, corresponding to a molecular disorganization of these fibers caused by collagenolysis.