Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Calcitonin gene-related peptide (CGRP) and adrenomedullin (ADM) are potent vasodilators in humans and improved myocardial ischemia is observed after CGRP administration. Receptors for CGRP and ADM were already identified in heart. Receptor activity-modifying proteins (RAMPs) determine the ligand specificity of the calcitonin receptor-like receptor (CRLR); co-expression of RAMP1 and CRLR results in a CGRP receptor, whereas the association of RAMP2 or RAMP3 with CRLR gives an ADM receptor. As CGRP and ADM may play a beneficial role in heart failure, we investigated whether the CGRP and ADM receptors are upregulated in chronic heart failure. We have used semi-quantitative RT-PCR and Western-blot analysis to detect and quantify the mRNA and the protein of RAMP1 and RAMP3 in both atria and ventricles of failing hearts 6 months after aortic banding in rats. Our results showed for the first time an up-regulation of RAMP1 and RAMP3 mRNAs and proteins in this model of cardiac failure. No change was observed in mRNAs coding for CRLR, RAMP2, RDC1 (canine orphan receptor), and ADM. The present results suggested after congestive heart failure in adult rats, an up-regulation of the CGRP receptor (by an increase in RAMP1 that is associated with CRLR) in atria and ventricles and of ADM receptor (by increased RAMP3 expression that is associated with CRLR) in atria. These findings support a functional role for CGRP and ADM receptors to compensate the chronic heart failure in rats.
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PMID:Increased myocardial expression of RAMP1 and RAMP3 in rats with chronic heart failure. 1205 17

In this work we aimed to observe (1) the changes in adrenomedullin (AM) and its receptor system - calcitonin receptor-like receptor (CRLR) and receptor activity modifying proteins (RAMPs) - in myocardial ischemic injury and (2) the response of injuried myocardia to AM and the phosphorylation of Akt to illustrate the protective mechanism of AM in ischemic myocardia. Male SD rats were subcutaneously injected with isoproterenol (ISO) to induce myocardial ischemia. The mRNA levels of AM, CRLR, RAMP1, RAMP2 and RAMP3 were determined by RT-PCR. Protein levels of Akt, phosphor-Akt, CRLR, RAMP1, RAMP2 and RAMP3 were assayed by Western blot. Results showed that, compared with that of the controls, ISO-treated rats showed lower cardiac function and myocardial injury. The mRNA relative amount of AM, CRLR, RAMP1, RAMP2 and RAMP3 in the myocardia of ISO-treated rats was increased. The elevated mRNA levels of CRLR, RAMP1, RAMP2 and RAMP3 were positively correlated with AM content in injured myocardia. The protein levels of CRLR, RAMP1, RAMP2 and RAMP3 in injured myocardia were increased compared with that of control myocardia. AM-stimulated cAMP generation in myocardia was elevated in the ISO group, and was antagonized by AM(22-52) and CGRP(8-37). Western blot analyses revealed that AM significantly enhanced Akt phosphorylation in injured myocardia, which was blocked by pretreatment with AM(22-52) or CGRP(8-37). Ischemia-injured myocardia hyper-expressed AM and its receptors - CRLR, RAMP1, RAMP2 and RAMP3 - and the response of ischemic myocardia to AM was potentiated, and the level of Akt phosphorylation was also increased, which suggests that changes in cardiac AM/AM receptor might play an important role in the pathogenesis of myocardial ischemic injury.
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PMID:The myocardial response to adrenomedullin involves increased cAMP generation as well as augmented Akt phosphorylation. 1730 19

Intermedin (IMD), a new calcitonin/calcitonin gene-related peptide family peptide with vasodilatory and positive inotropic properties, has multiple functions in regulating cardiovascular homeostasis and is of particular interest in the pathophysiology of myocardial ischemia/reperfusion (MI/R). We created a mouse model of MI/R by ligating the cardiac left anterior descending artery to study the possible pathophysiological role of IMD and its receptor complexes in MI/R. Compared with the control, infarcted mice showed increased content, mRNA and protein expression of IMD in plasma and cardiac tissue. The mRNA expression of the receptor activity-modifying protein 3 (RAMP3) gene increased very early, and the calcitonin receptor-like receptor and RAMP2 mRNA levels increased later after reperfusion. However, the RAMP1 gene expression did not change. The tissue IMD content was positively correlated with the diastolic blood pressure and negatively correlated with pulse pressure. In addition, exogenous IMD treatment significantly ameliorated the MI/R injury by rescuing the pulse pressure, inhibiting neutrophil infiltration in the peri-infarction area, and decreasing the creatine kinase and lactate dehydrogenase activities in plasma. Our results indicated that IMD was upregulated in the ischemic myocardium and may induce important beneficial cytoprotection against cardiac ischemic injury.
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PMID:Intermedin is upregulated and has protective roles in a mouse ischemia/reperfusion model. 1968 Feb 58