Acute actions of thyroid hormone on blood vessel biochemistry and physiology

Purpose of review Description of the progress about the vascular effects promoted by thyroid hormones. Recent findings Over the past few years, a number of studies have shown that in addition to genomic effects on blood vessels, thyroid hormones exert extranuclear nongenomic effects on vascular smooth muscle cells and endothelium. These nongenomic effects occur rapidly and do not involve thyroid hormone response elements-mediated transcriptional events. In this context, the genomic and nongenomic events promoted by thyroid hormones act in concert to control the vascular hemodynamic and regulate the cardiovascular function. Summary Considering the antiatherogenic property of thyroid hormones and the rapid effects produced by this molecule as a vasodilator, including that in the coronary bed, a better understanding of the molecular mechanisms involved in its action may contribute to the development of drugs that can be clinically used to increase the known benefits promoted by thyroid hormones in cardiovascular physiology.

Retinoic Acid and VEGF Delay Smooth Muscle Relative to Endothelial Differentiation to Coordinate Inner and Outer Coronary Vessel Wall Morphogenesis

Rationale: Major coronary vessels derive from the proepicardium, the cellular progenitor of the epicardium, coronary endothelium, and coronary smooth muscle cells (CoSMCs). CoSMCs are delayed in their differentiation relative to coronary endothelial cells (CoEs), such that CoSMCs mature only after CoEs have assembled into tubes. The mechanisms underlying this sequential CoE/CoSMC differentiation are unknown. Retinoic acid (RA) is crucial for vascular development and the main RA-synthesizing enzyme is progressively lost from epicardially derived cells as they differentiate into blood vessel types. In parallel, myocardial vascular endothelial growth factor (VEGF) expression also decreases along coronary vessel muscularization. Objective: We hypothesized that RA and VEGF act coordinately as physiological brakes to CoSMC differentiation. Methods and Results: In vitro assays (proepicardial cultures, cocultures, and RALDH2 [retinaldehyde dehydrogenase-2]/VEGF adenoviral overexpression) and in vivo inhibition of RA synthesis show that RA and VEGF act as repressors of CoSMC differentiation, whereas VEGF biases epicardially derived cell differentiation toward the endothelial phenotype. Conclusion: Experiments support a model in which early high levels of RA and VEGF prevent CoSMC differentiation from epicardially derived cells before RA and VEGF levels decline as an extensive endothelial network is established. We suggest this physiological delay guarantees the formation of a complex, hierarchical, tree of coronary vessels. (Circ Res. 2010;107:204-216.)

Subepithelial connective tissue graft for root coverage in smokers and non-smokers: A clinical and histologic controlled study in humans

Background: The aim of this study was to evaluate root coverage of gingival recessions and to compare graft vascularization in smokers and non-smokers. Methods: Thirty subjects, 15 smokers and 15 non-smokers, were selected. Each subject had one Miller Class I or II recession in a non-molar tooth. Clinical measurements of probing depth (PD), relative clinical attachment level (CAL), gingival recession (GR), and width of keratinized tissue (KT) were determined at baseline and 3 and 6 months after surgery. The recessions were treated surgically with a coronally positioned flap associated with a subepithelial connective tissue graft. A small portion of this graft was prepared for immunohistochemistry. Blood vessels were identified and counted by expression of factor VIII-related antigen-stained endothelial cells. Results: Intragroup analysis showed that after 6 months there a was gain in CAL, a decrease in GR, and an increase in KT for both groups (P<0.05), whereas changes in PD were not statistically significant. Smokers had less root coverage than non-smokers (58.02% +/- 19.75% versus 83.35% +/- 18.53%; P<0.05). Furthermore, the smokers had more GR (1.48 +/- 0.79 mm versus 0.52 +/- 0.60 mm) than the nonsmokers (P<0.05). Histomorphometry of the donor tissue revealed a blood vessel density of 49.01 +/- 11.91 vessels/200x field for non-smokers and 36.53 +/- 10.23 vessels/200x field for smokers (P<0.05). Conclusion: Root coverage with subepithelial connective tissue graft was negatively affected by smoking, which limited and jeopardized treatment results.

Light, electron microscopy and histopathology of Myxobolus salminus n. sp., a parasite of Salminus brasiliensis from the Brazilian Pantanal

In this report, we describe the morphology and histopathology of Myxobolus salminus n. sp., a parasite of the gill filaments of wild Salminus brasiliensis (dourado) from the Brazilian Pantanal. The small polysporic plasmodia were similar to 100 mu m in diameter and the development was asynchronous. The mature spores were oval to pear shaped and had a smooth wall. The spore measurements were (mean +/- S.D., with range in parentheses): length 10.1 +/- 0.4 mu m (9.6-10.5), width 6.1 +/- 0.4 mu m (5.8-6.6) and thickness 5.0 +/- 0.6 mu m (4.7-5.3). The polar capsules were elongated and of equal size: length 4.6 +/- 0.2 mu m (4.3-4.8) and width 1.7 +/- 0.1 mu m (1.5-1.9). The histological analysis revealed numerous plasmodia in the blood vessels of the gill filaments. The site of parasite development was the wall of the large-caliber blood vessel of the gill filament, with progressive growth towards the lumen, resulting in the obstruction of blood flow, congestion and perivascular edema. The ultrastructural study revealed that the plasmodial wall was composed of two membranes, had numerous pinocytic canals and was in direct contact with the basement membrane of the vessel. The development of the parasite was asynchronous, with mature spores, immature spores and young developmental stages randomly distributed throughout the plasmodium. The prevalence of the parasite was 4.4%. with male and female fish being infected. (C) 2009 Elsevier B.V. All rights reserved.

Fractal structures in stenoses and aneurysms in blood vessels

Recent advances in the field of chaotic advection provide the impetus to revisit the dynamics of particles transported by blood flow in the presence of vessel wall irregularities. The irregularity, being either a narrowing or expansion of the vessel, mimicking stenoses or aneurysms, generates abnormal flow patterns that lead to a peculiar filamentary distribution of advected particles, which, in the blood, would include platelets. Using a simple model, we show how the filamentary distribution depends on the size of the vessel wall irregularity, and how it varies under resting or exercise conditions. The particles transported by blood flow that spend a long time around a disturbance either stick to the vessel wall or reside on fractal filaments. We show that the faster flow associated with exercise creates widespread filaments where particles can get trapped for a longer time, thus allowing for the possible activation of such particles. We argue, based on previous results in the field of active processes in flows, that the non-trivial long-time distribution of transported particles has the potential to have major effects on biochemical processes occurring in blood flow, including the activation and deposition of platelets. One aspect of the generality of our approach is that it also applies to other relevant biological processes, an example being the coexistence of plankton species investigated previously.