Matrix metalloproteinase-9 and tissue inhibitor metalloproteinase-1 levels in essential hypertension. Relationship to left ventricular mass and anti-hypertensive therapy.
To test the hypothesis that the activity of enzymes degrading the extracellular matrix in hypertensive patients are abnormal, and that the treatment of hypertension will normalise these abnormalities, we measured the serum levels of metalloproteinase MMP-9, and its inhibitor, tissue metalloproteinase inhibitor (TIMP-1). Thirty-two patients with untreated hypertension (BP 168/96) had significantly lower levels of both MMP-9 and TIMP-1 when compared to 24 matched normotensive controls (BP 123/80) (P<0.001). There was no significant correlation between MMP-9 and TIMP-1 levels (P>0.2). In the patients, there were no significant correlations observed between left ventricular mass, Doppler V(E)/V(A) ratio (an index of diastolic function), blood pressure, left ventricular mass index and either MMP-9 or TIMP-1 levels (all P=NS). Levels of MMP-9 and TIMP-1 were not significantly altered after 2 months of antihypertensive treatment of 29 patients despite mean blood pressure falling from 170/96 to 143/85 mmHg (P<0.001). Correspondingly, there were also no significant alterations in indices of diastolic function and left ventricular mass. Our study suggests that the proteolytic activities of MMP-9 and TIMP-l are depressed in hypertensive patients and were not significantly affected by short-term antihypertensive treatment. The relationship between collagen metabolism in hypertensive subjects, especially in those with cardiac hypertrophy, and the effects of treatment needs to be further explored in larger trials over a longer period of time.
Li-Saw-Hee
F L
FL
Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, B18 7QH, Birmingham, UK.
Edmunds
E
E
Blann
A D
AD
Beevers
D G
DG
Lip
G Y
GY
D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001794:Blood Pressure; D003094:Collagen / Q000378:metabolism*; D015150:Echocardiography, Doppler; D004656:Enalapril / Q000627:therapeutic use; D004797:Enzyme-Linked Immunosorbent Assay; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000201:enzymology* / Q000378:metabolism / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000175:diagnosis / Q000209:etiology; D019808:Losartan / Q000627:therapeutic use; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D016277:Ventricular Function, Left
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D019715:Tissue Inhibitor of Metalloproteinase-1; D004656:Enalapril; D003094:Collagen; D020780:Matrix Metalloproteinase 9; D019808:Losartan