The effect of valvular regurgitation on plasma Cardiotrophin-1 in patients with normal left ventricular systolic function.
BACKGROUND
Cardiotrophin-1 (CT-1), a member of the interleukin-6 related cytokine family that act via the gp130 signalling pathway, has been shown to stimulate the assembly of sarcomeric units in series in cardiomyocytes resulting in eccentric hypertrophy, ventricular dilatation and finally loss of function. In situations of volume overload a similar form of eccentric hypertrophy occurs with time.


OBJECTIVE
We hypothesised that plasma CT-1 would be raised in patients with significant mitral, tricuspid and/or aortic regurgitation (MR/TR or AR, respectively) when compared to those with no (or mild) valvular regurgitant lesion.


METHODS
A novel competitive immunoluminometric assay using an in-house polyclonal antibody to amino acids 105-120 of the CT-1 sequence was developed. Seventy-eight patients (31 male, mean+/-S.D. age 63.5+/-17.9 years), all with normal left ventricular systolic function were studied. Results are expressed as mean+/-S.D. fmol/ml.


RESULTS
Sixty-three subjects had no significant valvular lesion, seven had moderate/severe MR, nine had moderate/severe TR and four had moderate/severe AR. These subjects had CT-1 concentrations of 53. 3+/-23.2, 90.5+/-44.4, 72.6+/-43.8 and 48.4+/-24.4, respectively (P=0.02, ANOVA). Mean log CT-1 was higher in those with moderate/severe MR when compared to those without a significant regurgitant valvular lesion (P<0.03). The only predictor of moderate/severe MR was log CT-1 (P=0.004).


CONCLUSIONS
These results suggest that plasma CT-1 is raised in those patients with moderate/severe MR in the presence of normal left ventricular systolic function. This secretion of CT-1 could potentially be the cause of ventricular dilatation and subsequent loss of contractile function in these patients. It also offers the intriguing possibility that plasma CT-1 could be used to monitor progression of mitral regurgitation biochemically.
Talwar
S
S
Department of Medicine and Therapeutics, University of Leicester, Leicester, UK.
Squire
I B
IB
Davies
J E
JE
Ng
L L
LL
D001022:Aortic Valve Insufficiency / Q000097:blood*; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008944:Mitral Valve Insufficiency / Q000097:blood*; D013599:Systole / Q000502:physiology; D014262:Tricuspid Valve Insufficiency / Q000097:blood*; D016277:Ventricular Function, Left / Q000502:physiology*
D016207:Cytokines; C092073:cardiotrophin 1