Relationships between plasma levels of matrix metalloproteinases and neurohormonal profile in patients with heart failure.
BACKGROUND
Both neurohormonal derangements and alterations in the myocardial extracellular matrix are thought to contribute to adverse ventricular remodelling that results in worsening heart failure (HF). There is also emerging preclinical information to suggest that these signalling pathways mutually regulate in HF.


OBJECTIVE
To assess the relationships between plasma levels of matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinase (TIMP), and neurohormonal profiles in chronic HF.


RESULTS
In this substudy of 184 HF patients enrolled in the Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) trial, plasma norepinephrine and epinephrine were measured with HPLC; atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), angiotensin II, aldosterone, and endothelin-1 were measured with immunoassays; MMP-2, MMP-9, and TIMP-1 were measured with 2-site sandwich ELISA assays. We used Spearman's rank correlation to examine the relationships between plasma MMP and neurohormone levels. Circulating ANP, BNP, and endothelin-1 levels were positively correlated with MMP-2 and TIMP-1 levels. Plasma level of aldosterone showed a weak positive correlation with MMP-9, but there was no significant correlation between angiotensin II, epinephrine or norepinephrine and MMP-2, MMP-9, or TIMP-1.


CONCLUSIONS
These findings suggest that specific neurohormones and extracellular matrix modulators may play a coordinated role in the pathogenesis of HF.
Yan
Andrew T
AT
Terrence Donnelly Heart Centre, Division of Cardiology, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
Yan
Raymond T
RT
Spinale
Francis G
FG
Afzal
Rizwan
R
Gunasinghe
Himali R
HR
Stroud
Robert E
RE
McKelvie
Robert S
RS
Liu
Peter P
PP
D000368:Aged; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D009320:Atrial Natriuretic Factor / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D019332:Endothelin-1 / Q000097:blood; D005109:Extracellular Matrix / Q000502:physiology; D005260:Female; D006333:Heart Failure / Q000097:blood*; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000097:blood*; D008875:Middle Aged; D018377:Neurotransmitter Agents / Q000097:blood*; D019714:Tissue Inhibitor of Metalloproteinases / Q000097:blood*
D019332:Endothelin-1; D018377:Neurotransmitter Agents; D019714:Tissue Inhibitor of Metalloproteinases; D000804:Angiotensin II; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D020782:Matrix Metalloproteinases