Gene Expression, Function and Ischemia Tolerance in Male and Female Rat Hearts After Sub-Toxic Levels of Angiotensin II

To examine the response to chronic high-dose angiotensin II (Ang II) and a proposed milder response in female hearts with respect to gene expression and ischemic injury. Female and male litter–matched rats were treated with 400 ng kg−1 min−1 Ang II for 14 days. Hearts were isolated, subjected to 30-min ischemia and 30-min reperfusion in combination with functional monitoring and thereafter harvested for gene expression, WB and histology. Ang II-treated hearts showed signs of non-hypertrophic remodeling and had significantly higher end diastolic pressure after reperfusion, but no significant gender difference was detected. Ang II increased expression of genes related to heart function (ANF, β-MCH, Ankrd-1, PKC-α, PKC-δ TNF-α); fibrosis (Col I-α1, Col III-α1, Fn-1, Timp1) and apoptosis (P53, Casp-3) without changing heart weight but with 68% increase in collagen content. High (sub-toxic) dose of Ang II resulted in marked heart remodeling and diastolic dysfunction after ischemia without significant myocyte hypertrophy or ventricular chamber dilatation. Although there were some gender-dependent differences in gene expression, female gender did not protect against the overall response

Simulated weightlessness changes the cytoskeleton and extracellular matrix protein in papillary thyroid carcinoma cells

Studies of astronauts, experimental animals, and cells have shown that, after spaceflights, the function of the thyroid is altered by low-gravity conditions. The objective of this study was to investigate the cytoskeleton and extracellular matrix (ECM) protein synthesis of papillary thyroid cancer cells grown under zero g. We investigated alterations of ONCO-DG 1 cells exposed to simulated microgravity on a three-dimensional random-positioning machine (clinostat) for 30 min, 24 h, 48 h, 72 h, and 120 h (n=6, each group). ONCO-DG 1 cells grown under microgravity exhibited early alterations of the cytoskeleton and formed multicellular spheroids. The cytoskeleton was disintegrated, and nuclei showed morphological signs of apoptosis after 30 min. At this time, vimentin was increased. Vimentin and cytokeratin were highly disorganized, and microtubules (alpha-tubulin) did not display their typical radial array. After 48 h, the cytoskeletal changes were nearly reversed. The formation of multicellular spheroids continued. In parallel, the accumulation of ECM components, such as collagen types I and III, fibronectin, chondroitin sulfate, osteopontin, and CD44, increased. The levels of both transforming growth factor beta-1 (TGF-beta(1)) and TGF-beta receptor type II proteins were elevated from 24 h until 120 h clinorotation. Gene expression of TGF-beta(1) was clearly enhanced during culture under zero g. The amount of E-cadherin was enhanced time-dependently. We suggest that simulated weightlessness rapidly affects the cytoskeleton of papillary thyroid carcinoma cells and increases the amount of ECM proteins in a time-dependent manner

Intraluminal application of vascular endothelial growth factor enhances healing of microvascular anastomosis in a rat model

Background: Early reconstitution after injury to the endothelium is an important feature for reducing a number of vessel wall pathologies. We investigated the effect of vascular endothelial growth factor ( VEGF) and its impact on the vascular remodeling process and reendothelialization after microsurgery. Methods and Results: Microvascular anastomosis was performed in the rat femoral artery. One group was treated with intraluminal administration of VEGF and the other with vehicle. We investigated morphological, ultrastructural and immunohistochemical changes of the vascular wall and the reendothelialization process. After 10 days, reendothelialization was significantly faster in VEGF-treated rats. Transmission electron microscopy revealed a complete healing in contrast to vehicle-treated vessels. Moreover, extracellular matrix proteins, such as fibronectin, collagen types I, III and IV, were significantly increased. Furthermore, VEGF treatment significantly induced VEGF receptor 2, flk-1, osteopontin and TGF-β(1) proteins. Conclusions: Our data clearly document for the first time that intraluminal treatment with VEGF is beneficial to the healing process in vascular microsurgery. Osteopontin and TGF-β(1), both induced by VEGF, may play an important role in the vascular remodeling process. Our results provide clear evidence that VEGF application may represent a useful strategy in accelerating reendothelialization and improving vascular healing after microsurgery. Copyright (C) 2005 S. Karger AG, Basel