<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi mathvariant="bold">β</mml:mi></mml:math>-Adrenergic Receptor-Stimulated Cardiac Myocyte Apoptosis: Role of <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi mathvariant="bold">β</mml:mi></mml:math>1 Integrins

Amin, Parthiv; Singh, Mahipal; Singh, Krishna

doi:10.1155/2011/179057

Cited by 29 publications

(28 citation statements)

References 99 publications

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“…Prolonged stimulation of the ␤-adrenergic neurohormonal axis contributes to the progression of heart failure and mortality in animal models and human patients (3,13). Catecholamines, released during heightened adrenergic drive, accumulate in the interstitial space of the heart (6,8).…”

Section: Discussionmentioning

confidence: 99%

Exogenous ubiquitin modulates chronic β-adrenergic receptor-stimulated myocardial remodeling: role in Akt activity and matrix metalloproteinase expression

Daniels

Foster

Yakoob

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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β-Adrenergic receptor (β-AR) stimulation increases extracellular ubiquitin (UB) levels, and extracellular UB inhibits β-AR-stimulated apoptosis in adult cardiac myocytes. This study investigates the role of exogenous UB in chronic β-AR-stimulated myocardial remodeling. l-Isoproterenol (ISO; 400 μg·kg(-1)·h(-1)) was infused in mice in the presence or absence of UB (1 μg·g(-1)·h(-1)). Left ventricular (LV) structural and functional remodeling was studied 7 days after infusion. UB infusion enhanced serum UB levels. In most parts, UB alone had no effect on morphometric or functional parameters. Heart weight-to-body weight ratios were increased to a similar extent in the ISO and UB + ISO groups. Echocardiographic analyses showed increased percent fractional shortening, ejection fraction, and LV circumferential stress and fiber-shortening velocity in the ISO group. These parameters were significantly lower in UB + ISO vs. ISO. Isovolumic contraction and relaxation times and ejection time were significantly lower in ISO vs. UB + ISO. The increase in the number of TUNEL-positive myocytes and fibrosis was significantly higher in ISO vs. UB + ISO. Activation of Akt was higher, whereas activation of GSK-3β and JNKs was lower in UB + ISO vs ISO. Expression of MMP-2, MMP-9, and TIMP-2 was higher in UB + ISO vs ISO. In isolated cardiac fibroblasts, UB enhanced expression of MMP-2 and TIMP-2 in the presence of ISO. Neutralizing UB antibodies negated the effects of UB on MMP-2 expression, whereas recombinant UB enhanced MMP-2 expression. UB activated Akt, and inhibition of Akt inhibited UB + ISO-mediated increases in MMP-2 expression. Thus, exogenous UB plays an important role in β-AR-stimulated myocardial remodeling with effects on LV function, fibrosis, and myocyte apoptosis.

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Section: Discussionmentioning

confidence: 99%

Exogenous ubiquitin modulates chronic β-adrenergic receptor-stimulated myocardial remodeling: role in Akt activity and matrix metalloproteinase expression

Daniels

Foster

Yakoob

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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“…Inhibition of MMP-2 in myocytes is shown to decrease β-adrenergic receptor-stimulated apoptosis, and JNK-dependent mitochondrial death is considered as the major pathway [54]. Activation of MMP-2 cleaves the nuclear poly(ADP-ribose)polymerase (PARP) and results in apoptosis via mitochondrial pathway releasing apoptosis-inducing factor from the mitochondria [55–57].…”

Section: Mmps and Apoptosismentioning

confidence: 99%

Matrix metalloproteinases in diabetic retinopathy: potential role of MMP-9

Kowluru

Zhong

Santos

2012

Expert Opinion on Investigational Drugs

140

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Introduction Diabetic retinopathy remains one of the most feared complications of diabetes. Despite extensive research in the field, the molecular mechanism responsible for the development of this slow progressing disease remains unclear. In the pathogenesis of diabetic retinopathy, mitochondria are damaged and inflammatory mediators are elevated before the histopathology associated with the disease can be observed. Matrix metalloproteinases (MMPs) regulate a variety of cellular functions including apoptosis and angiogenesis. Diabetic environment stimulates the secretion of several MMPs that are considered to participate in complications, including retinopathy, nephropathy and cardiomyopathy. Patients with diabetic retinopathy and also animal models have shown increased MMP-9 and MMP-2 in their retina and vitreous. Recent research has shown that MMPs have dual role in the development of diabetic retinopathy; in the early stages of the disease (pre-neovascularization), MMP-2 and MMP-9 facilitate the apoptosis of retinal capillary cells, possibly via damaging the mitochondria, and in the later phase, they help in neovascularization. Areas covered This article reviews the literature to evaluate the role of MMPs, especially MMP-9, in the development of diabetic retinopathy, and presents existing evidence that the inhibitors targeted toward MMP-9, depending on the duration of diabetes at the times their administration could have potential to prevent the progression of this blinding disease, and protect the vision loss. Expert opinion Inhibitors of MMPs could have dual role: in the early stages of the diseases, inhibit capillary cell apoptosis, and if the disease has progressed to the angiogenic stage, inhibit the growth of new vessels.

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“…The costamere complex includes β1 and α7 integrins that span the plasma membrane [20]. The β1 integrins in particular are important surface receptors in cardiomyocytes, regulating cell matrix interactions [21] and playing a role in cytoprotection [22]. Integrins are anchored to the z-disk by structural proteins including vinculin, talin, desmin, and zyxin [14].…”

Section: Introductionmentioning

confidence: 99%

Substrate stiffness affects sarcomere and costamere structure and electrophysiological function of isolated adult cardiomyocytes

Galie

Khalid

Carnahan

et al. 2013

Cardiovascular Pathology

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Introduction The mechanical environment is a key regulator of function in cardiomyocytes. We studied the role of substrate stiffness on the organization of sarcomeres and costameres in adult rat cardiomyocytes, and further examined the resulting changes in cell shortening and calcium dynamics. Methods Cardiomyocytes isolated from adult rats were plated on laminin-coated polydimethylsiloxane substrates of defined stiffness (255 kPa, 117 kPa, 27 kPa, and 7 kPa) for 48 h. Levels of α-actinin and β1 integrins were determined by immunofluoresence imaging and immunoblotting, both in the absence and presence of the phosphatase inhibitor calyculin A. Quantitative RT-PCR was used to measure message levels of key structural proteins (α-actinin, α7 integrin, β1 integrin, vinculin). Sarcomere shortening and calcium dynamics were measured at 2, 24, and 48 hours. Results Overall cardiomyocyte morphology was similar on all substrates. However, well organized sarcomere structures were observed on only the stiffest (255 kPa) and the most compliant (7 kPa) substrates. Levels of α-actinin in cells were the same on all substrates, while message levels of structural proteins were upregulated on substrates of intermediate stiffness. Inhibition of phosphatase activity blocked the degradation of contractile structures, but altered overall cardiomyocyte morphology. Shortening and calcium dynamics also were dependent on substrate stiffness, however there was no clear causative relationship between the phenomena. Conclusions Extracellular matrix stiffness can affect structural remodeling by adult cardiomyocytes, and the resulting contractile activity. These findings illuminate changes in cardiomyocyte function in cardiac fibrosis, and may suggest cardiac-specific phosphatases as a target for therapeutic intervention

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β-Adrenergic Receptor-Stimulated Cardiac Myocyte Apoptosis: Role of β1 Integrins

Cited by 29 publications

References 99 publications

Exogenous ubiquitin modulates chronic β-adrenergic receptor-stimulated myocardial remodeling: role in Akt activity and matrix metalloproteinase expression

Exogenous ubiquitin modulates chronic β-adrenergic receptor-stimulated myocardial remodeling: role in Akt activity and matrix metalloproteinase expression

Matrix metalloproteinases in diabetic retinopathy: potential role of MMP-9

Substrate stiffness affects sarcomere and costamere structure and electrophysiological function of isolated adult cardiomyocytes

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