Model for environmental heat damage of the blood vessel barrier

Abstract

Environmental heat stress may result in loss of fluid from the vascular space, which can lead to circulatory shock. Since the endothelium serves as the blood vessel barrier between the vascular and interstitial spaces, direct heat damage to this tissue may contribute to such fluid loss. This study modeled heat influences on the actin cytoskeletal proteins that provide the tensile forces that sustain endothelial junctional integrity or barrier function. Heat effects on bovine aortic endothelial cell (BAEC) F-actin and F-actin stress fibers (FASFs) were correlated with intercellular permeability (IP). F-actin concentration and FASF distribution were analyzed by quantitation of the specific binding of rhodamine phalloidin (RP) to F-actin and by observing the fluorescence of RP-FASF complexes, respectively. Dextran fluorescein IP was determined. The IP was elevated (p < 0.05) at 43 degrees C, but not at 41 degrees C. At 43 degrees C, BAECs were rounded and had disrupted FASFs and diminished cell-to-cell apposition. Similar cells were seen at 41 degrees C, but these were interspersed among FASF-containing cells to sustain apposition. Thus, disruption of FASFs correlated with increases in IP. F-actin was increased (p < 0.05) after hyperthermia. Since G-actin is more susceptible to irreversible heat denaturation, F-actin sustainment may function to preserve the actin pool and prevent irrevocable loss of the blood vessel barrier after heat stress.

Peritoneal mesothelioma treated by induction chemotherapy, cytoreductive surgery, and intraperitoneal hyperthermic perfusion

“…The employment of heat, as a fundamental component of this new therapeutic methodology, is justified by its own cancericidal property and chemosensitivity-modulating capacity. The biophysical effects of hyperthermia are not completely understood, but probably include membrane protein denaturation, increased vascular permeability [18,19], alterations in multimolecular complexes such as the insulin receptor [20] and in the cytoskeleton [18], and changes in enzyme complexes for DNA synthesis and repair [21]. Moreover, the architecture of the vasculature in solid tumors is chaotic, resulting in regions with low pH, hypoxia, and low glucose level [22].…”

Flunarizine pretreatment attenuates hyperthermia-induced extravasation in rats

“…Previously, hyperthermia has been associated with increases in endothelial permeability [7,23,24]. Fever level (38-41°C) hyperthermia enhances lymphocyte binding to endothelial cells via L-selectin-mediated adhesion and subsequent increased lymphocyte migration from the vasculature [31].…”

“…F-actin stress fibers are cytoskeletal structures that provide the tensile forces necessary to maintain junctional integrity between cells [29,30]. Hyperthermia alters the structure of the endothelial cell cytoskeleton, thus changing the cell's shape [7,23]. When the actin microfibrils in endothelial cells are disrupted, the cells contract, resulting in the formation of a gap between cells and concomitantly increased vascular permeability and edema [7].…”

“…In vitro studies have shown that, providing the hyperthermia does not exceed a threshold level (43°C [23], 44°C [7]), the endothelial pathology appears to be reversible within 24 h. Therefore, pharmacological treatment of hyperthermia that sustains the vascular integrity (with cooling to halt further damage) may prevent irreversible shock, minimize the need for large volumes of intravenous fluids and the consequent cardiac and renal strain, and preclude potential pulmonary edema.…”

Thymosinβ4 has a major role in dermal burn wound healing that involves actin cytoskeletal remodelling via heat-shock protein 70

“…Analysis of FGAR was implemented to confirm any changes in the actin cytoskeleton, in order to provide more quantitative details than are available through analysis of microphotography, overcoming limitations such as the inability to perform numerical quantification. One previous study found that heat injury damaged the blood vessel barrier between the vascular and interstitial spaces via an accumulation of F‐actin (DuBose et al ., ). The present study is the first to demonstrate that T β 4 markedly induced HSP70 and attenuated the FGAR.…”