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Prelamin A mediates myocardial inflammation in dilated and HIV-Associated cardiomyopathies

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Prelamin A mediates myocardial inflammation in dilated and HIV-Associated cardiomyopathies. / Brayson, Daniel; Frustaci, Andrea; Verardo, Romina; Chimenti, Cristina; Russo, Matteo Antonio; Hayward, Robert; Ahmad, Sadia Munir; Vizcay-barrena, Gema; Protti, Andrea; Zammit, Peter S.; Dos Remedios, Cristobal G.; Ehler, Elisabeth; Shah, Ajay M.; Shanahan, Catherine M.

In: JCI Insight, Vol. 4, No. 22, e126315, 14.11.2019.

Research output: Contribution to journalArticle

Harvard

Brayson, D, Frustaci, A, Verardo, R, Chimenti, C, Russo, MA, Hayward, R, Ahmad, SM, Vizcay-barrena, G, Protti, A, Zammit, PS, Dos Remedios, CG, Ehler, E, Shah, AM & Shanahan, CM 2019, 'Prelamin A mediates myocardial inflammation in dilated and HIV-Associated cardiomyopathies', JCI Insight, vol. 4, no. 22, e126315. https://doi.org/10.1172/jci.insight.126315

APA

Brayson, D., Frustaci, A., Verardo, R., Chimenti, C., Russo, M. A., Hayward, R., ... Shanahan, C. M. (2019). Prelamin A mediates myocardial inflammation in dilated and HIV-Associated cardiomyopathies. JCI Insight, 4(22), [e126315]. https://doi.org/10.1172/jci.insight.126315

Vancouver

Brayson D, Frustaci A, Verardo R, Chimenti C, Russo MA, Hayward R et al. Prelamin A mediates myocardial inflammation in dilated and HIV-Associated cardiomyopathies. JCI Insight. 2019 Nov 14;4(22). e126315. https://doi.org/10.1172/jci.insight.126315

Author

Brayson, Daniel ; Frustaci, Andrea ; Verardo, Romina ; Chimenti, Cristina ; Russo, Matteo Antonio ; Hayward, Robert ; Ahmad, Sadia Munir ; Vizcay-barrena, Gema ; Protti, Andrea ; Zammit, Peter S. ; Dos Remedios, Cristobal G. ; Ehler, Elisabeth ; Shah, Ajay M. ; Shanahan, Catherine M. / Prelamin A mediates myocardial inflammation in dilated and HIV-Associated cardiomyopathies. In: JCI Insight. 2019 ; Vol. 4, No. 22.

Bibtex Download

@article{5730398a41c644269bd5e48746fa54fd,
title = "Prelamin A mediates myocardial inflammation in dilated and HIV-Associated cardiomyopathies",
abstract = "Cardiomyopathies are complex heart muscle diseases that can be inherited or acquired. Dilated cardiomyopathy can result from mutations in LMNA, encoding the nuclear intermediate filament proteins lamin A/C. Some LMNA mutations lead to accumulation of the lamin A precursor, prelamin A, which is disease causing in a number of tissues, yet its impact upon the heart is unknown. Here, we discovered myocardial prelamin A accumulation occurred in a case of dilated cardiomyopathy, and we show that a potentially novel mouse model of cardiac-specific prelamin A accumulation exhibited a phenotype consistent with inflammatory cardiomyopathy, which we observed to be similar to HIV-Associated cardiomyopathy, an acquired disease state. Numerous HIV protease therapies are known to inhibit ZMPSTE24, the enzyme responsible for prelamin A processing, and we confirmed that accumulation of prelamin A occurred in HIV+ patient cardiac biopsies. These findings (a) confirm a unifying pathological role for prelamin A common to genetic and acquired cardiomyopathies; (b) have implications for the management of HIV patients with cardiac disease, suggesting protease inhibitors should be replaced with alternative therapies (i.e., nonnucleoside reverse transcriptase inhibitors); and (c) suggest that targeting inflammation may be a useful treatment strategy for certain forms of inherited cardiomyopathy.",
author = "Daniel Brayson and Andrea Frustaci and Romina Verardo and Cristina Chimenti and Russo, {Matteo Antonio} and Robert Hayward and Ahmad, {Sadia Munir} and Gema Vizcay-barrena and Andrea Protti and Zammit, {Peter S.} and {Dos Remedios}, {Cristobal G.} and Elisabeth Ehler and Shah, {Ajay M.} and Shanahan, {Catherine M.}",
year = "2019",
month = "11",
day = "14",
doi = "10.1172/jci.insight.126315",
language = "English",
volume = "4",
journal = "JCI Insight",
issn = "2379-3708",
publisher = "The American Society for Clinical Investigation",
number = "22",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Prelamin A mediates myocardial inflammation in dilated and HIV-Associated cardiomyopathies

AU - Brayson, Daniel

AU - Frustaci, Andrea

AU - Verardo, Romina

AU - Chimenti, Cristina

AU - Russo, Matteo Antonio

AU - Hayward, Robert

AU - Ahmad, Sadia Munir

AU - Vizcay-barrena, Gema

AU - Protti, Andrea

AU - Zammit, Peter S.

AU - Dos Remedios, Cristobal G.

AU - Ehler, Elisabeth

AU - Shah, Ajay M.

AU - Shanahan, Catherine M.

PY - 2019/11/14

Y1 - 2019/11/14

N2 - Cardiomyopathies are complex heart muscle diseases that can be inherited or acquired. Dilated cardiomyopathy can result from mutations in LMNA, encoding the nuclear intermediate filament proteins lamin A/C. Some LMNA mutations lead to accumulation of the lamin A precursor, prelamin A, which is disease causing in a number of tissues, yet its impact upon the heart is unknown. Here, we discovered myocardial prelamin A accumulation occurred in a case of dilated cardiomyopathy, and we show that a potentially novel mouse model of cardiac-specific prelamin A accumulation exhibited a phenotype consistent with inflammatory cardiomyopathy, which we observed to be similar to HIV-Associated cardiomyopathy, an acquired disease state. Numerous HIV protease therapies are known to inhibit ZMPSTE24, the enzyme responsible for prelamin A processing, and we confirmed that accumulation of prelamin A occurred in HIV+ patient cardiac biopsies. These findings (a) confirm a unifying pathological role for prelamin A common to genetic and acquired cardiomyopathies; (b) have implications for the management of HIV patients with cardiac disease, suggesting protease inhibitors should be replaced with alternative therapies (i.e., nonnucleoside reverse transcriptase inhibitors); and (c) suggest that targeting inflammation may be a useful treatment strategy for certain forms of inherited cardiomyopathy.

AB - Cardiomyopathies are complex heart muscle diseases that can be inherited or acquired. Dilated cardiomyopathy can result from mutations in LMNA, encoding the nuclear intermediate filament proteins lamin A/C. Some LMNA mutations lead to accumulation of the lamin A precursor, prelamin A, which is disease causing in a number of tissues, yet its impact upon the heart is unknown. Here, we discovered myocardial prelamin A accumulation occurred in a case of dilated cardiomyopathy, and we show that a potentially novel mouse model of cardiac-specific prelamin A accumulation exhibited a phenotype consistent with inflammatory cardiomyopathy, which we observed to be similar to HIV-Associated cardiomyopathy, an acquired disease state. Numerous HIV protease therapies are known to inhibit ZMPSTE24, the enzyme responsible for prelamin A processing, and we confirmed that accumulation of prelamin A occurred in HIV+ patient cardiac biopsies. These findings (a) confirm a unifying pathological role for prelamin A common to genetic and acquired cardiomyopathies; (b) have implications for the management of HIV patients with cardiac disease, suggesting protease inhibitors should be replaced with alternative therapies (i.e., nonnucleoside reverse transcriptase inhibitors); and (c) suggest that targeting inflammation may be a useful treatment strategy for certain forms of inherited cardiomyopathy.

UR - http://www.scopus.com/inward/record.url?scp=85077742360&partnerID=8YFLogxK

U2 - 10.1172/jci.insight.126315

DO - 10.1172/jci.insight.126315

M3 - Article

VL - 4

JO - JCI Insight

JF - JCI Insight

SN - 2379-3708

IS - 22

M1 - e126315

ER -

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