The role of the nuclear lamins in the pathogenesis of heart failure in patients undergoing cardiac transplantation.
The nuclear lamins A/C play a critical role in maintaining the structure of the nuclear lamina and the organization of various proteins, such as emerin. These protein levels may play roles in the pathogenesis and clinical evolution of both ischemic (ICM) and dilated (DCM) cardiomyopathy. We evaluated the nuclear morphology of cardiomyocytes and determine lamins A/C and emerin levels among DCM and ICM heart failure patients compared with control human hearts. We determined protein levels by Western blots using mouse monoclonal antibodies in 23 explanted human hearts. Lamin A was increased in failing hearts but significantly different only among the DCM compared with the control group: mean, 236 +/- 51 vs 100 +/- 34; (P < .05). However, lamin C in the DCM group was near control values and significantly decreased in the ICM cohort compared to controls 75 +/- 7 versus 100 +/- 3 (P < .05). No alterations in emerin levels were observed in ICM or DCM, compared with controls. In conclusion, hearts with ICM or DCM showed different alterations in the nuclear morphology of cardiomyocytes; ICM patients had decreased lamin C, whereas DCM patients had increased lamin A. These changes affecting nuclear structure and function may have prognostic implications, for cardiomyopathy etiology.
Cortés
R
R
Unidad de Cardiocirculación, Centro de Investigación, Hospital Universitario La Fe, Valencia, Spain.
Roselló-Lletí
E
E
Rivera
M
M
Martínez-Dolz
L
L
Azorín
I
I
Salvador
A
A
Portolés
M
M
D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal; D017023:Coronary Angiography; D005260:Female; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000209:etiology*; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D034904:Lamin Type A / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008875:Middle Aged; D011183:Postoperative Complications / Q000209:etiology*; D011506:Proteins / Q000032:analysis; D018608:Ultrasonography, Doppler
D000911:Antibodies, Monoclonal; D034904:Lamin Type A; D011506:Proteins; C440308:lamin C