Cardiac and vascular hypertrophy in Fabry disease: evidence for a new mechanism independent of blood pressure and glycosphingolipid deposition.
OBJECTIVE
Fabry disease is an X-linked disorder resulting from alpha-galactosidase A deficiency. The cardiovascular findings include left ventricular hypertrophy (LVH) and increased intima-media thickness of the common carotid artery (CCA IMT). The current study examined the possible correlation between these parameters. To corroborate these clinical findings in vitro, plasma from Fabry patients was tested for possible proliferative effect on rat vascular smooth muscle cells (vascular smooth muscle cell [VSMC]) and mouse neonatal cardiomyocytes.


RESULTS
Thirty male and 38 female patients were enrolled. LVH was found in 60% of men and 39% of women. Increased CCA IMT was equally present in males and females. There was a strong positive correlation between LV mass and CCA IMT (r2=0.27; P<0.0001). VSMC and neonatal cardiomyocyte proliferative response in vitro correlated with CCA IMT (r2=0.39; P<0.0004) and LV mass index (r2=0.19; P=0.028), respectively.


CONCLUSIONS
LVH and CCA IMT occur concomitantly in Fabry suggesting common pathogenesis. The underlying cause may be a circulating growth-promoting factor whose presence has been confirmed in vitro.
Barbey
Frédéric
F
Nephrology Department, University Hospital, Lausanne, Switzerland.
Brakch
Noureddine
N
Linhart
Ales
A
Rosenblatt-Velin
Nathalie
N
Jeanrenaud
Xavier
X
Qanadli
Salah
S
Steinmann
Beat
B
Burnier
Michel
M
Palecek
Tomas
T
Bultas
Jan
J
Hayoz
Daniel
D
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001794:Blood Pressure; D001798:Blood Proteins / Q000494:pharmacology; D017536:Carotid Artery, Common / Q000503:physiopathology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004452:Echocardiography; D000795:Fabry Disease / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D005260:Female; D006028:Glycosphingolipids / Q000378:metabolism*; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000473:pathology; D051381:Rats; D017539:Tunica Intima / Q000473:pathology / Q000503:physiopathology; D017540:Tunica Media / Q000473:pathology / Q000503:physiopathology
D001798:Blood Proteins; D006028:Glycosphingolipids