Expression of P2X4R mRNA and protein in rats with hypobaric hypoxia-induced pulmonary hypertension.

BACKGROUND: The experimental pulmonary hypertension that develops in hypobaric hypoxia is characterized by structural remodeling of the heart. The P2X4 receptor (P2X4R) controls vascular tone and vessel remodeling in several blood vessels, and it has emerged as a key factor in the enhancement of cardiovascular performance. METHODS AND RESULTS: To study the possible effects of hypobaric hypoxia on the P2X4R-synthesis system, 150 male Wistar rats were housed in a chamber at the equivalent of the 5,500 m altitude level for 21 days. After 14 days' exposure to hypobaric hypoxia, pulmonary arterial pressure (PAP) was significantly increased. In the right ventricle (RV) of the heart, P2X4R expression was significantly increased on days 1 and 14 (mRNA) and on days 7 and 21 (protein) of hypobaric hypoxic exposure. Immunohistochemical staining for P2X4R protein became more intense in RV in the late phase of exposure. These changes in P2X4R synthesis in RV occurred alongside the increase in PAP. In addition, P2X1R and P2Y2R mRNA levels in the RV were significantly increased on days 1, 14, and 21, and day 5, respectively, of exposure. The level of P2X1R protein in the RV was significantly increased on day 21 of exposure. CONCLUSIONS: Conceivably, P2 receptors, including P2X4R and P2X1R, might play roles in modulating the RV hypertrophy that occurs due to pulmonary hypertension in hypobaric hypoxia.

Malignant amelanotic melanoma of the pleura without primary skin lesion:an autopsy case report.

Melanoma metastasizing to the lungs is common, but primary pulmonary or pleural melanoma is extremely rare. We present an autopsy case of malignant melanoma of the pleura without primary skin lesion in a 49-year-old man. A mass found in the right chest was diagnosed as spindle cell sarcoma by antemortem fine-needle aspiration cytology. At autopsy, a yellow-white tumor located primarily in the right visceral pleura (diagnosed as an amelanotic melanoma) was found to have invaded into the right lung, right parietal pleura, and right diaphragm, and to have metastasized into the left lung and visceral pleura, thyroid, and left adrenal gland. No primary site was found. The tumor cells were positive for S100 and focally positive for HMB-45, but negative for other markers. Immuno-histochemical examination for S100 and HMB-45 would thus appear to be useful for the diagnosis of an amelanotic melanoma.

Proteomic analysis of the lung in rats with hypobaric hypoxia-induced pulmonary hypertension.

Experimental pulmonary hypertension that develops in hypobaric hypoxia is characterized by structural remodeling of the lung. Proteomics - which may be the most powerful way to uncover unknown remodeling proteins involved in enhancing cardiovascular performance - was used to study 150 male Wistar rats housed for up to 21 days in a chamber at the equivalent of 5500 m altitude level. After 14 days' exposure to hypobaric hypoxia, pulmonary arterial pressure (PAP) was significantly increased. In lung tissue, about 140 matching protein spots were found among 8 groups (divided according to their hypobaric period) by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) (pH4.5-pH6.5, 30 kDa-100 kDa). In hypobaric rats, three spots were increased two-fold or more (vs. control rats) in two-dimensional differential in-gel electrophoresis (2D-DIGE). The increased proteins were identified, by matrix-assisted laser desorption ionization time of flight (MALDI-TOF), as one isoform of heat shock protein 70 (HSP70) and two isoforms of protein disulfide isomerase associated 3. This result was confirmed by Western blotting analysis of 2D-PAGE. Conceivably, HSP70 and PDIA3 may play roles in modulating the lung structural remodeling that occurs due to pulmonary hypertension in hypobaric hypoxia.