Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P39060 (endostatin)
 2,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies demonstrate low serum levels of 25-hydroxyvitamin D in patients with congestive heart failure (CHF). Although this may in part reflect reduced capacity for outdoor exercise, the possibility that poor vitamin D status increases risk for left ventricular hypertrophy (LVH), and its common sequel CHF, merits consideration. In cardiomyocytes, hormones which activate protein kinase C (PKC) -- including norepinephrine, angiotensin II, and endostatin, implicated in the pathogenesis of LVH -- induce a hypertrophic response analogous to that seen in LVH. Transgenic mice overexpressing PKC-beta2 or its upstream activator Galphaq in cardiac myofibers develop a syndrome similar to LVH. Parathyroid hormone (PTH) also activates Galphaq and PKC in cardiomyocytes, and provokes the expected hypertrophic response. Both primary and secondary hyperparathyroidism are associated with high risk for LVH. Moreover, in uncomplicated essential hypertension, left ventricular mass index has been shown to correlate very tightly with serum PTH levels, independent of blood pressure. This latter finding suggests that variations of PTH within the normal range can influence induction of LVH in at-risk subjects. If so, nutritional and lifestyle measures which modulate PTH secretion may have an impact on LVH risk. PTH secretion should be down-regulated by good vitamin D status -- achieved through supplementation or regular uv exposure -- and by vegan diets moderately low in bioavailable phosphate. Although high calcium intakes can likewise suppress PTH, they also boost renin secretion, which could have a countervailing effect on risk for LVH. Whether these nutritional measures do indeed influence LVH risk could be examined in prospective studies targeting patients at high risk, such as hypertensives.
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PMID:Nutritional modulation of parathyroid hormone secretion may influence risk for left ventricular hypertrophy. 1578 May 3

Severe pulmonary hypertension (SPH) is characterized by precapillary arteriolar lumen obliteration, dramatic right ventricular hypertrophy, and pericardial effusion. Our recently published rat model of SPH recapitulates major components of the human disease. We used this model to develop new treatment strategies for SPH. SPH in rats was induced using VEGF receptor blockade in combination with chronic hypoxia. A large variety of drugs used in this study, including anticancer drugs (cyclophosphamide and paclitaxel), the angiotensin-converting enzyme inhibitor lisinopril, the antiangiogenic agent thalidomide, and the peroxisome proliferator-actived receptor-gamma agonist PGJ2, failed to decrease mean pulmonary artery pressure (PAP) or right ventricular hypertrophy. In contrast, treatment of rats with established SPH with simvastatin markedly reduced mean PAP and right ventricular hypertrophy, and this reduction was associated with caspase-3 activation and pulmonary microvascular endothelial cell apoptosis. Simvastatin partially restored caveolin-1, caveolin-2, and phospho-caveolin expression in vessel walls. In rat primary pulmonary microvascular endothelial cells, simvastatin induced caspase 3 activation and Rac 1 expression while suppressing Rho A and attenuated levels of Akt and ERK phosphorylation. We conclude that simvastatin is effective in inducing apoptosis in hyperproliferative pulmonary vascular lesions and could be considered as a potential drug for treatment of human SPH.
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PMID:Simvastatin causes endothelial cell apoptosis and attenuates severe pulmonary hypertension. 1669 53