Cardioprotective effects of verapamil on myocardial structure and function in a murine model of chronic Trypanosoma cruzi infection (Brazil Strain): an echocardiographic study

Chandra, Madhulika; Shirani, Jamshid; Shtutin, Vitaliy; Weiss, Louis M.; Factor, Stephen M.; Petkova, Stefka B.; Rojkind, Marcos; Domı́nguez-Rosales, José Alfredo; Jelicks, Linda A.; Morris, Stephen A.; Wittner, Murray; Tanowitz, Herbert B.

doi:10.1016/s0020-7519(01)00320-4

Cited by 57 publications

(72 citation statements)

References 33 publications

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“…Thus, we opted to describe the presented effects as resulting from Se treatment. Chandra et al 2002, Huang et al 2003. Treatment with Se for 76-98 days reversed atrial alterations, observed in all infected non-treated mice; this effect was manifested as a normalization of the P wave duration that is typically prolonged in infected-untreated mice.…”

Section: Discussionmentioning

confidence: 84%

The benefits of using selenium in the treatment of Chagas disease: prevention of right ventricle chamber dilatation and reversion of Trypanosoma cruzi-induced acute and chronic cardiomyopathy in mice

Souza¹,

Jelicks²,

Tanowitz

et al. 2010

Mem. Inst. Oswaldo Cruz

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Section: Discussionmentioning

confidence: 84%

The benefits of using selenium in the treatment of Chagas disease: prevention of right ventricle chamber dilatation and reversion of Trypanosoma cruzi-induced acute and chronic cardiomyopathy in mice

Souza¹,

Jelicks²,

Tanowitz

et al. 2010

Mem. Inst. Oswaldo Cruz

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“…However, by 4 months of age, the Cav-3 KO hearts showed an even more dramatic increase in left ventricular wall thickness (ϳ20%), indicating that this is a progressive cardiomyopathic phenotype. Interestingly, the increase in left ven- (32). Importantly, the heart rates of all animals tested were not statistically different, thereby allowing for meaningful comparisons.…”

Section: Cav-3 Ko Mice Do Not Express Caveolin-3 In the Heart Andmentioning

confidence: 95%

“…Transthoracic Echocardiography-Transthoracic echocardiography was performed as described previously (32). Echocardiography was performed with mice in a supine position on a heating pad set at 38°C.…”

Section: Non-invasive Cardiac Imagingmentioning

confidence: 99%

Caveolin-3 Knock-out Mice Develop a Progressive Cardiomyopathy and Show Hyperactivation of the p42/44 MAPK Cascade

Woodman

Park

Cohen

et al. 2002

Journal of Biological Chemistry

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268

241

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A growing body of evidence suggests that muscle cell caveolae may function as specialized membrane microdomains in which the dystrophin-glycoprotein complex and cellular signaling molecules reside. Caveolin-3 (Cav-3) is the only caveolin family member expressed in striated muscle cell types (cardiac and skeletal). Interestingly, skeletal muscle fibers from Cav-3 (؊/؊) knockout mice show a number of myopathic changes, consistent with a mild-to-moderate muscular dystrophy phenotype. However, it remains unknown whether a loss of Cav-3 affects the phenotypic behavior cardiac myocytes in vivo. Here, we present a detailed characterization of the hearts of Cav-3 knock-out mice. We show that these mice develop a progressive cardiomyopathic phenotype. At four months of age, Cav-3 knock-out hearts display significant hypertrophy, dilation, and reduced fractional shortening, as revealed by gated cardiac MRI and transthoracic echocardiography. Histological analysis reveals marked cardiac myocyte hypertrophy, with accompanying cellular infiltrates and progressive interstitial/peri-vascular fibrosis. Interestingly, loss of Cav-3 expression in the heart does not change the expression or the membrane association of the dystrophin-glycoprotein (DG) complex. However, a marker of the DG complex, ␣-sarcoglycan, was specifically excluded from lipid raft domains in the absence of Cav-3. Because activation of the Ras-p42/44 MAPK pathway in cardiac myocytes can drive cardiac hypertrophy, we next assessed the activation state of this pathway using a phospho-specific antibody probe. We show that p42/44 MAPK (ERK1/2) is hyperactivated in hearts derived from Cav-3 knock-out mice. These results are consistent with previous in vitro data demonstrating that caveolins may function as negative regulators of the p42/44 MAPK cascade. Taken together, our data argue that loss of Cav-3 expression is sufficient to induce a molecular program leading to cardiac myocyte hypertrophy and cardiomyopathy.

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“…29 Echocardiography was performed with mice in supine position on a heating pad set at 38°C. Light anesthesia was achieved using isoflurane inhalation.…”

Section: Transthoracic Echocardiographymentioning

confidence: 99%

“…Light anesthesia was achieved using isoflurane inhalation. 29 Continuous, standard electrocardiograms were taken from electrodes placed on the extremities. Echocardiographic images were obtained using an annular array, broadband, 10/5 MHz transducer attached to an HDI 5000 CV ultrasound system (Advanced Technology Laboratories, Bothel, WA).…”

Section: Transthoracic Echocardiographymentioning

confidence: 99%

Caveolin-1/3 Double-Knockout Mice Are Viable, but Lack Both Muscle and Non-Muscle Caveolae, and Develop a Severe Cardiomyopathic Phenotype

Park

Woodman

Schubert

et al. 2002

The American Journal of Pathology

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191

147

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The caveolin gene family consists of caveolins 1, 2, and 3. Caveolins 1 and 2 are co-expressed in many cell types, such as endothelial cells, fibroblasts, smooth muscle cells and adipocytes, where they form a heteroligomeric complex. In contrast, the expression of caveolin-3 is muscle-specific. Thus, the expression of caveolin-1 is required for caveolae formation in nonmuscle cells, while the expression of caveolin-3 drives caveolae formation in striated muscle cell types (cardiac and skeletal). To create a truly caveolae-deficient mouse, we interbred Cav-1 null mice and Cav-3 null mice to generate Cav-1/Cav-3 double-knockout (Cav-1/3 dKO) mice. Here, we report that Cav-1/3 dKO mice are viable and fertile, despite the fact that they lack morphologically identifiable caveolae in endothelia, adipocytes, smooth muscle cells, skeletal muscle fibers, and cardiac myocytes. We also show that these mice are deficient in all three caveolin gene products, as caveolin-2 is unstable in the absence of caveolin-1. Interestingly, Cav-1/3 dKO mice develop a severe cardiomyopathy. Caveolae are 50-to 100-nm omega-shaped invaginations of the plasma membrane found in various tissue types. The principal structural proteins of caveolar membranes are encoded by the caveolin gene family (caveolin-1, -2, and -3). Caveolin-1 and -2 are co-expressed in numerous tissue types, with particularly high expression in adipocytes, endothelial cells, fibroblasts, and epithelial cells.1,2 Caveolin-3, on the other hand, is muscle-specific, being highly expressed in all muscle tissues, such as skeletal muscle, diaphragm, and heart. 3,4 Caveolin-1 and -3 form ϳ350-kd homo-oligomers made up of ϳ14 -16 caveolin monomers. These homooligomers serve as the basic structural units that drive the formation of caveolae membranes. In contrast, Cav-2 either homodimerizes or forms high molecular mass hetero-oligomers with Cav-1.5-7 Cav-1 and Cav-3 are both independently necessary and sufficient to drive caveolae formation in heterologous expression systems, while Cav-2 requires the presence of Cav-1 for proper membrane targeting and stabilization. In the absence of

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Cardioprotective effects of verapamil on myocardial structure and function in a murine model of chronic Trypanosoma cruzi infection (Brazil Strain): an echocardiographic study

Cited by 57 publications

References 33 publications

The benefits of using selenium in the treatment of Chagas disease: prevention of right ventricle chamber dilatation and reversion of Trypanosoma cruzi-induced acute and chronic cardiomyopathy in mice

The benefits of using selenium in the treatment of Chagas disease: prevention of right ventricle chamber dilatation and reversion of Trypanosoma cruzi-induced acute and chronic cardiomyopathy in mice

Caveolin-3 Knock-out Mice Develop a Progressive Cardiomyopathy and Show Hyperactivation of the p42/44 MAPK Cascade

Caveolin-1/3 Double-Knockout Mice Are Viable, but Lack Both Muscle and Non-Muscle Caveolae, and Develop a Severe Cardiomyopathic Phenotype

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