Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0151814 (coronary occlusion)
 3,687 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ischemic preconditioning (PC) is an adaptive response to transient myocardial ischemia that protects the heart from subsequent ischemia/reperfusion (I/R) injury. However, the mechanisms underlying its cardioprotective effects remain unclear. Myocardium of adult male C57/BL6 mice, preconditioned by 6 cycles of 4 minute coronary occlusion and reperfusion, showed nuclear translocation of ATF3 and ATF6 and PERK phosphorylation 30 min after PC. The abundance of ER proteins, ATF3 and ATF4 was increased 24h after PC; however, there was no evidence of IRE-1 activation in WT or ER-stress activated indicator (ERAI) mice expressing XBP-1-Venus fusion protein. PC-induced nuclear translocation of ATF3 was attenuated in transgenic mice with cardiac-restricted overexpression of inducible ATF6. Ischemic PC increased the abundance of inducible nitric oxide synthase, cyclooxygenase-2, heme oxygenase-1 and aldose reductase to levels similar between WT and ATF3-null hearts; however, the increase in IL-6 and ICAM-1 was exaggerated in ATF3-null hearts. Genetic deletion of ATF3 did not increase infarct size in non-preconditioned hearts but abolished the cardioprotective effects of PC. Larger infarct size in preconditioned ATF3-null hearts was associated with greater neutrophil infiltration in the myocardium, but no ATF3-dependent changes in the total or relative abundance of inflammatory monocytes were observed. Ischemic PC activates the unfolded protein response (UPR) and the activation of ATF3 by ER stress is essential for the cardioprotective effects of late PC.
 ...
PMID:Endoplasmic reticulum stress-dependent activation of ATF3 mediates the late phase of ischemic preconditioning. 2515 53

Mammalian cardiomyocytes exit the cell cycle shortly after birth. As a result, an occurrence of coronary occlusion-induced myocardial infarction often results in heart failure, postinfarction LV dilatation, or death, and represents one of the most significant public health morbidities worldwide. Interestingly however, the hearts of neonatal pigs have been shown to regenerate following an acute myocardial infarction (MI) occuring on postnatal day 1 (P1); a recovery period which is accompanied by an increased expression of markers for cell-cycle activity, and suggests that early postnatal myocardial regeneration may be driven in part by the MI-induced proliferation of pre-existing cardiomyocytes. In this study, we identified signaling pathways known to regulate the cell cycle, and determined of these, the pathways persistently upregulated in response to MI injury. We identified five pathways (mitogen associated protein kinase [MAPK], Hippo, cyclic [cAMP], Janus kinase/signal transducers and activators of transcription [JAK-STAT], and Ras) which were comprehensively upregulated in cardiac tissues collected on day 7 (P7) and/or P28 of the P1 injury hearts. Several of the initiating master regulators (e.g., CSF1/CSF1R, TGFB, and NPPA) and terminal effector molecules (e.g., ATF4, FOS, RELA/B, ITGB2, CCND1/2/3, PIM1, RAF1, MTOR, NKF1B) in these pathways were persistently upregulated at day 7 through day 28, suggesting there exists at least some degree of regenerative activity up to 4 weeks following MI at P1. Our observations provide a list of key regulators to be examined in future studies targeting cell-cycle activity as an avenue for myocardial regeneration.
 ...
PMID:Identifying the key regulators that promote cell-cycle activity in the hearts of early neonatal pigs after myocardial injury. 3273 Feb 72