Sustained augmentation of cardiac α1A-adrenergic drive results in pathological remodeling with contractile dysfunction, progressive fibrosis and reactivation of matricellular protein genes

Chaulet, Hervé; Lin, Fang; Guo, Jia; Owens, W Andrew; Michalicek, Jan; Kesteven, Scott; Guan, Ziyao; Prall, Owen W.J.; Mearns, Bryony M.; Feneley, Michael P.

doi:10.1016/j.yjmcc.2006.01.015

Cited by 38 publications

(42 citation statements)

References 49 publications

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“…To clarify this, we testified the PE effect on [Ca 2+ ] i in freshly isolated and cultured NRVM for <1 day and ≥2 day for compatibility with the aortic myocytes. As expected, all of the cardiomyocytes from either group [20,24,[31][32][33] . Similar to other studies [9,13,14,24,32] , we combined selective antagonists for each subtype with selective agonists to distinguish among contributions of the different subtypes to vasoconstriction.…”

Section: Ar Activationsupporting

confidence: 70%

“…However, unlike the situation for α 1A -and α 1B -ARs, information regarding α 1D -AR cellular functions and their underlying regulatory mechanisms is scant because of the difficulties in obtaining sufficient function in native or recombinant cells in vitro, raising the question of whether manifestations of the α 1D -ARs expressed in vitro are, in fact, representative of the physiological situation [9,11,12] . In the current study, we sought to determine the causes for the inconsistencies in α 1 AR regulatory effects on vascular contractility between the in vivo and in vitro studies by comparing α 1 AR-mediated Ca 2+ signaling and its subcellular distribution in native rat aortic and cardiac myocytes (α 1D -AR and α 1A -AR subtypes are known to contribute mainly to α 1 adrenergic mediation of constriction in the rat aorta [13,14] and cardiac muscle [20][21][22][23][24] , respectively).…”

Section: Introductionmentioning

confidence: 99%

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α1D-Adrenergic receptor insensitivity is associated with alterations in its expression and distribution in cultured vascular myocytes

et al. 2009

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Aim: It is unclear why α 1D -adrenergic receptors (α 1D -ARs) play a critical role in the mediation of peripheral vascular resistance and blood pressure in situ but function inefficiently when studied in vitro. The present study examined the causes for these inconsistencies in native α 1 -adrenergic functional performance between the vascular smooth muscle and myocytes. Methods: The α 1 -adrenergic mediated contraction, Ca 2+ signaling and the subcellular receptor distribution were evaluated using the Fluo-4, BODIPY-FL prazosin and subtype-specific antibodies. Results: Rat aortic rings and freshly dissociated myocytes displayed contractile and increased intracellular Ca 2+ responses to stimulation with phenylephrine (PE, 10 µmol), respectively. However, the PE-induced responses disappeared completely in cultured aortic myocytes, whereas PE-enhanced Ca 2+ transients were seen in cultured rat cardiac myocytes. Further studies indicated that α 1D -ARs, the major receptor subtype responsible for the α 1 -adrenergic regulation of aortic contraction, were distributed both intracellularly and at the cell membrane in freshly dispersed aortic myocytes, similar to the α 1A -AR subcellular localization in the cultured cardiomyocytes. In the cultured aortic myocytes, however, in addition to a marked decrease in their protein expression relative to the aorta, most labeling signals for α 1D -ARs were found in the cytoplasm. Importantly, treating the culture medium with charcoal/dextran caused the reappearance of α 1D -ARs at the cell surface and a partial restoration of the Ca 2+ signal response to PE in approximately 30% of the cultured cells. Conclusion: Reduction in α 1D -AR total protein expression and disappearance from the cell surface contribute to the insensitivity of cultured vascular smooth muscle cells to α 1 -adrenergic receptor activation.

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Section: Ar Activationsupporting

confidence: 70%

Section: Introductionmentioning

confidence: 99%

α1D-Adrenergic receptor insensitivity is associated with alterations in its expression and distribution in cultured vascular myocytes

et al. 2009

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“…Cardiac myocyte-specific transgenic overexpression of the WT a 1 A-subtype, even at very high levels (148-to 170-fold), does not alter heart size, although a 1 A transgenic mice eventually develop dilated cardiomyopathy and die prematurely (Lin et al, 2001;Chaulet et al, 2006). On the other hand, transgenic overexpression of constitutively active mutant (CAM) a 1 A with the endogenous a 1 A-promoter induces cardiac hypertrophy without an effect on systemic blood pressure (Papay et al, 2013).…”

Section: A a 1 -Adrenergic Receptors Activate Physiologic Or Adaptivmentioning

confidence: 99%

Cardiac Alpha₁-Adrenergic Receptors: Novel Aspects of Expression, Signaling Mechanisms, Physiologic Function, and Clinical Importance

et al. 2013

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“…Hence, the grade of occlusion in IRA should be shown in all of the patients with acute coronary syndromes. The expression of tenascin-C increases the early phase of fibrosis and cardiac repair after cardiac injury 20) . It has also been observed in human coronary atherosclerotic plaque 7) but the relation between higher tenascin-C levels and the coronary lesion's anatomy was indeterminate.…”

Section: Discussionmentioning

confidence: 99%

The Relationship between Tenascin-C Levels and the Complexity of Coronary Lesion after Myocardial Infarction

Çelik

2011

JAT

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Aim:The increase of tenascin-C levels after myocardial infarction has been demonstrated by previous studies. The relationship between tenascin-C and the grade of stenosis in the infarct-related coronary artery was indeterminate. The aim of this study was to evaluate the relationship between tenascin-C levels and total occlusion after acute myocardial infarction. Method: Fifty-nine patients with subacute anterior myocardial infarction were divided into two groups according to their having a totally or subtotally occluded left anterior desending artery. Plasma tenascin-C, troponin , CK-MB, uric acid, mean platelet volume, and lipid profile levels were also measured. Results: The history of the smoking rate, hypertension and diabetes mellitus were similar in both groups. Hemoglobin, mean platelet volume, serum creatinine, CK-MB, troponin I, serum lipid profile and uric acid levels were similar in the two groups. The CRP and tenascin-C levels were significantly higher in the total occlusion group. Tenascin-C levels were highest in patients with proximal LAD total occlusion and lowest in patients with subtotal LAD occlusion. The tenascin-C levels were correlated with the grade of stenosis (r 0.602, p 0.001). Conclusion: This study demonstrates that higher tenascin-C levels were related with the total occlusion and inflammation after MI. J Atheroscler Thromb, 2011; 18:693-697.

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Sustained augmentation of cardiac α1A-adrenergic drive results in pathological remodeling with contractile dysfunction, progressive fibrosis and reactivation of matricellular protein genes

Cited by 38 publications

References 49 publications

α1D-Adrenergic receptor insensitivity is associated with alterations in its expression and distribution in cultured vascular myocytes

α1D-Adrenergic receptor insensitivity is associated with alterations in its expression and distribution in cultured vascular myocytes

Cardiac Alpha₁-Adrenergic Receptors: Novel Aspects of Expression, Signaling Mechanisms, Physiologic Function, and Clinical Importance

The Relationship between Tenascin-C Levels and the Complexity of Coronary Lesion after Myocardial Infarction

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Sustained augmentation of cardiac α1A-adrenergic drive results in pathological remodeling with contractile dysfunction, progressive fibrosis and reactivation of matricellular protein genes

Cited by 38 publications

References 49 publications

α1D-Adrenergic receptor insensitivity is associated with alterations in its expression and distribution in cultured vascular myocytes

α1D-Adrenergic receptor insensitivity is associated with alterations in its expression and distribution in cultured vascular myocytes

Cardiac Alpha1-Adrenergic Receptors: Novel Aspects of Expression, Signaling Mechanisms, Physiologic Function, and Clinical Importance

The Relationship between Tenascin-C Levels and the Complexity of Coronary Lesion after Myocardial Infarction

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Product

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Cardiac Alpha₁-Adrenergic Receptors: Novel Aspects of Expression, Signaling Mechanisms, Physiologic Function, and Clinical Importance