Regional Changes in Angiotensin II Receptor Density after Experimental Myocardial Infarction

Lefroy, David; Wharton, John; Crake, Tom; Knock, Greg A.; Rutherford, Richard A.D.; Suzuki, Tak; Morgan, Kevin; Polak, Julia M.; Poole‐Wilson, Philip A.

doi:10.1006/jmcc.1996.0039

Cited by 69 publications

(39 citation statements)

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“…12,16,17 Recent studies have demonstrated that TIMI 2 grade flow after PCI, which we defined as angiographic no reflow, may be caused by microvascular dysfunction sustained in the ischemic region. 12,18 Many mechanisms have been postulated for this microvascular dysfunction, including free radicals, 19 -21 cardiac sympathetic reflexes with resulting ␣-adrenergic macrovascular and microvascular constriction, 16 regional changes in angiotensin II receptor density, 22 and selectin-regulated interactions between activated polymorphonuclear leukocytes and the endothelium. 23 In most of our no-reflow cases, however, there was TIMI 3 grade flow at some point before the no-reflow phenomenon, and subsequent ST segment re-elevation was observed immediately after angioplasty.…”

Section: Discussionmentioning

confidence: 99%

No-Reflow Phenomenon and Lesion Morphology in Patients With Acute Myocardial Infarction

et al. 2002

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Background-The no-reflow phenomenon is associated with poor functional and clinical outcomes for patients with acute myocardial infarction (AMI). In the era of primary intervention, accurately identifying lesions at high risk of no reflow is of crucial importance. At present, no study into the relationship between lesion morphology and no reflow has been performed. The aim of this study was to investigate the relationship between preintervention intravascular ultrasound (IVUS) lesion morphology and the no-reflow phenomenon. Methods and Results-This study comprised 100 consecutive patients with AMI who underwent preintervention IVUS and were successfully recanalized with primary balloon angioplasty or stenting. IVUS was again performed to identify and exclude any mechanical vessel obstruction in cases of thrombolysis in myocardial infarction flow grade 0, 1, or 2 after intervention in the absence of angiographic stenosis. Angiographic no reflow was seen in 13 patients (13%). Univariate analysis indicated that hypercholesterolemia, fissure and dissection, lipid pool-like image, lesion, and reference external elastic membrane cross-sectional area correlate with the no-reflow phenomenon. Multivariate logistic regression analysis showed that lipid pool-like image (PϽ0.05; odds ratio 118; 95% CI, 1.28 to 11 008) and lesion elastic membrane cross-sectional area (PϽ0.05; odds ratio 1.55; 95% CI 1.01 to 2.38) are independent predictive factors of no-reflow phenomenon after reperfusion for AMI. Conclusions-Large vessels with lipid pool-like image are at high risk for no reflow after primary intervention for AMI.Also, plaque content may play a role in damage to the microcirculation after primary intervention for AMI.

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Section: Discussionmentioning

confidence: 99%

No-Reflow Phenomenon and Lesion Morphology in Patients With Acute Myocardial Infarction

et al. 2002

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“…We also showed upregulation of ventricular AT 1 -R in hearts with AMI, consistent with the data previously demonstrated in animal studies. [33][34][35] The present human study was mainly carried out using autopsy samples obtained immediately after death. Ang II receptor levels and Na ϩ ,K ϩ -ATPase activities in samples obtained at operation or biopsy were very similar to those in autopsy samples, and also RNA quality, judging from 28S/18S ratio of rRNA and GAPDH mRNA, was high in autopsy samples.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II Type 2 Receptor Is Upregulated in Human Heart With Interstitial Fibrosis, and Cardiac Fibroblasts Are the Major Cell Type for Its Expression

Tsutsumi

Matsubara

Ohkubo

et al. 1998

Circulation Research

216

159

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Abstract-The expression pattern of angiotensin (Ang) II type 2 receptor (AT 2 -R) in the remodeling process of human left ventricles (LVs) remains poorly defined. We analyzed its expression at protein, mRNA, and cellular levels using autopsy, biopsy, or operation LV samples from patients with failing hearts caused by acute (AMI) or old (OMI) myocardial infarction and idiopathic dilated cardiomyopathy (DCM) and also examined functional biochemical responses of failing hearts to Ang II. In autopsy samples from the nonfailing heart group, the ratio of AT 1 -R and AT 2 -R was 59% and 41%, respectively. The expression of AT 2 -R was markedly increased in DCM hearts at protein (3.5-fold) and mRNA (3.1-fold) levels compared with AMI or OMI. AT 1 -R protein and mRNA levels in AMI hearts showed 1.5-and 2.1-fold increases, respectively, whereas in OMI and DCM hearts, AT 1 -R expression was significantly downregulated. AT 1 -R-mediated response in inositol phosphate production was significantly attenuated in LV homogenate from failing hearts compared with nonfailing hearts. AT 2 -R sites were highly localized in the interstitial region in either nonfailing or failing heart, whereas AT 1 -R was evenly distributed over myocardium at lower densities. Mitogen-activated protein kinase (MAPK) activation by Ang II was significantly decreased in fibroblast compartment from the failing hearts, and pretreatment with AT 2 -R antagonist caused an additional significant increase in Ang II-induced MAPK activity (36%). Cardiac hypertrophy suggested by atrial and brain natriuretic peptide levels was comparably increased in OMI and DCM, whereas accumulation of matrix proteins such as collagen type 1 and fibronectin was much more prominent in DCM than in OMI. These findings demonstrate that (1) AT 2 -R expression is upregulated in failing hearts, and fibroblasts present in the interstitial regions are the major cell type responsible for its expression, (2) AT 2 -R present in the fibroblasts exerts an inhibitory effect on Ang II-induced mitogen signals, and (3) AT 1 -R in atrial and LV tissues was downregulated during chronic heart failure, and AT 1 -R-mediated functional biochemical responsiveness was decreased in the failing hearts. Thus, the expression level of AT 2 -R is likely determined by the extent of interstitial fibrosis associated with heart failure, and the expression and function of AT 1 -R and AT 2 -R are differentially regulated in failing human hearts. (Circ Res. 1998;83:1035-1046.)Key Words: angiotensin II type 2 receptor Ⅲ AT 2 receptor Ⅲ angiotensin II type 1 receptor Ⅲ AT 1 receptor, angiotensin II T he presence of 2 isoforms of angiotensin (Ang) II receptor was originally proposed on the basis of differences in sensitivity of receptor-ligand binding to dithiothreitol. Ang type 2 receptor (AT 2 -R), which is insensitive to dithiothreitol and has a high affinity for PD123319 and CGP42112A, was isolated, and this receptor was shown to have the same seventransmembrane domain of AT 1 -R but only minimal homology (see Review i...

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“…117 Following MI in rodents, macrophages and myofibroblasts involved in tissue repair express renin,ACE and Ang II receptors, predominantly of the AT 1 -subtype. [118][119][120][121][122] This has implicated locallyproduced Ang II at sites of injury in regulating collagen turnover, which has been further suggested by the cardioprotective actions of losartan, an AT 1 -receptor antagonist, in attenuating fibrous tissue formation at, and remote to, the site MI. 123 Locallyproduced Ang II is also involved in regulating de novo ALDO production in the infarcted heart, 124 which likewise may contribute to tissue repair.…”

Section: Central Actions Of Aldosteronementioning

confidence: 99%

Toward a broader understanding of aldosterone in congestive heart failure

Weber

Sun

Wodi

et al. 2003

J Renin Angiotensin Aldosterone Syst

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Discovered some 50 years ago, aldosterone (ALDO) has come to be recognised as a mineralocorticoid hormone with well-known endocrine properties in epithelial cells that contribute to the pathophysiology of congestive heart failure. This includes Na + in such non-epithelial cells as peripheral blood mononuclear cells; its influence on endothelial cell function; and its central actions that involve regulation of cerebrospinal fluid composition produced by epithelial cells of the choroid plexus, activity of the hypothalamic paraventricular nucleus involved in Na + appetite, Na + and H 2 O excretion and sympathetic nerve activity, and the regulation of TNF-α production from central and/or peripheral sources. Extra-adrenal steroidogenesis and auto/paracrine properties of ALDO generated de novo in the cardiovasculature are now under investigation and preliminary findings suggest they contribute to tissue repair. The past decade has witnessed a revival of interest in this steroid molecule. In years to come, an even broader understanding of ALDO's contribution to the pathophysiology of congestive heart failure will undoubtedly emerge.

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Regional Changes in Angiotensin II Receptor Density after Experimental Myocardial Infarction

Cited by 69 publications

References 0 publications

No-Reflow Phenomenon and Lesion Morphology in Patients With Acute Myocardial Infarction

No-Reflow Phenomenon and Lesion Morphology in Patients With Acute Myocardial Infarction

Angiotensin II Type 2 Receptor Is Upregulated in Human Heart With Interstitial Fibrosis, and Cardiac Fibroblasts Are the Major Cell Type for Its Expression

Toward a broader understanding of aldosterone in congestive heart failure

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