Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0848237 (acute stress)
 4,619 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Toll-like receptors (TLRs) are a family of pattern-recognition receptors involved in innate immunity. Previous studies have shown that TLR2 inhibition protects the heart from acute stress, including myocardial infarction and doxorubicin-induced cardiotoxicity in animal models. However, the role of TLR2 in the development of aging-associated heart failure is not known. In this work, we studied aging-associated changes in structure and function of TLR2-deficient mice hearts. Whereas young TLR2-KO mice did not develop marked cardiac dysfunction, 8- and 12-month-old TLR2-KO mice exhibited spontaneous adverse cardiac remodeling and cardiac dysfunction in an age-dependent manner. The hearts of the 8-month-old TLR2-KO mice had increased fibrosis, cell death, and reactivation of fetal genes. Moreover, TLR2-KO hearts displayed reduced infiltration by macrophages, increased numbers of myofibroblasts and atrophic cardiomyocytes, and higher levels of the atrophy-related ubiquitin ligases MuRF-1 and atrogin-1. Mechanistically, TLR2 deficiency impaired the PI3K/Akt signaling pathway, leading to hyperactivation of the transcription factor Forkhead box protein O1 (FoxO1) and, in turn, to elevated expression of FoxO target genes involved in the regulation of muscle wasting and cell death. AS1842856-mediated chemical inhibition of FoxO1 reduced the expression of the atrophy-related ubiquitin ligases and significantly reversed the adverse cardiac remodeling while improving the contractile functions in the TLR2-KO mice. Interestingly, TLR2 levels decreased in hearts of older mice, and the activation of TLR1/2 signaling improved cardiac functions in these mice. These findings suggest that TLR2 signaling is essential for protecting the heart against aging-associated adverse remodeling and contractile dysfunction in mice.
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PMID:Toll-like receptor 2 deficiency hyperactivates the FoxO1 transcription factor and induces aging-associated cardiac dysfunction in mice. 2992 78

Copeptin is a precursor for arginine vasopressin which is usually elevated in acute stress and cardiac emergencies. Bisphenol A (BPA) is an ideal plasticizing factor used in manufacturing of plastics and epoxy resins. To evaluate the cardio toxicity of bisphenol A and to assess copeptin as a cardio toxic diagnostic and prognostic biomarker in Wistar rats. Sixty Wistar rats were classified into three groups: group I, naive group received regular diet and water; group II, vehicle group administered corn oil; and group III, each rat received BPA daily with (30 mg/kg/day S.C). After 4 weeks, blood samples were collected for estimating serum copeptin levels. Then, the hearts were subjected to histological, immunohistochemical, and electron microscopic examination. Cell suspensions from the hearts were examined to determine the extent of DNA damage by comet assay. Bisphenol A induced a significant increase in mean values of serum copeptin level, histopathological changes in the form of dilated congested blood vessels and extensive collagen fiber deposition in the myocardium. Ultrastructurally, disturbed indented nuclei, focal lysis of myofibrils, normal cross striations loss, mitochondrial swelling, and intercalated disks distortion were noticed. Immunohistochemical study showed a significant increase in TLR2 immunoreactions in the myocytes of BPA administered rats. In addition, comet assay showed that bisphenol A exposure produced DNA damage in cardiac cells. We concluded that bisphenol A has deleterious effects on cardiac tissues mean, while copeptin is a good diagnostic and prognostic biomarker.
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PMID:Role of copeptin as a novel biomarker of bisphenol A toxic effects on cardiac tissues: biochemical, histological, immunohistological, and genotoxic study. 3171 31