Tissue inhibitor of metalloproteinase-1 and matrix metalloproteinase-9 levels in patients with hypertension Relationship to tissue Doppler indices of diastolic relaxation.
BACKGROUND
Hypertension, hypertensive heart disease, and left ventricular (LV) hypertrophy are integral to symptomatic diastolic heart failure. Tissue inhibitor of metalloproteinase-1 (TIMP-1) is linked to extracellular matrix fibrosis and is elevated in hypertension. We hypothesized a link between circulating TIMP-1, matrix metalloproteinase-9 (MMP-9), and resting echocardiographic LV filling parameters using tissue Doppler parameters of diastolic (dys)function.


METHODS
Circulating MMP-9 and TIMP-1 levels were measured in citrated plasma by ELISA in 74 patients with hypertension (58 men, mean age 58 +/- 11 years) and 34 controls (23 men, mean age 53 +/- 13 years). All had confirmed normal short axis systolic contractility, with no significant wall motion abnormalities; the LV mass and standard resting tissue Doppler echocardiographic indices of diastolic function were also recorded.


RESULTS
Both MMP-9 and TIMP-1 levels were higher in the hypertensive group (P =.0039 and P =.0054, respectively). When compared to controls, hypertensive patients had a greater LV mass (P =.0054), and differences in many of the parameters reflecting diastolic dysfunction (controls versus hypertensives: E: 0.71 +/- 0.15 v 0.81 +/- 0.15 m/sec, P =.004; A: 0.66 +/- 0.12 v 0.81 +/- 0.16 m/sec, P <.0001; e': 0.12 (0.09-0.14) v 0.09 (0.07-0.10) m/sec, P =.0017; e'/a': 1.20 (1.00-1.80) v 0.88 (0.71-1.05), P <.0001; E/e': 6.54 (4.75-7.14) v 8.89 (7.55-10.75), P <.0001, respectively). Within the hypertensive cohort, only TIMP-1 levels correlated with LV mass (r = 0.271, P =.024), LV mass index (r = 0.323, P =.007), and tissue Doppler parameters of diastolic dysfunction, including e' (r = -0.338, P =.005), a' (r = -0.350, P =.005), and E/e' (r = 0.334, P =.005).


CONCLUSIONS
TIMP-1 is thought to increase tissue concentrations of collagen type I by preventing its breakdown by MMPs. Our findings therefore add weight to a hypothesis suggesting that TIMP-1 may be a key mediator of LV diastolic dysfunction through definition of ventricular matrix composition.
Tayebjee
Muzahir H
MH
Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, United Kingdom.
Nadar
Sunil K
SK
MacFadyen
Robert J
RJ
Lip
Gregory Y H
GY
D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use; D003430:Cross-Sectional Studies; D003971:Diastole; D015150:Echocardiography, Doppler; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006801:Humans; D006973:Hypertension / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D013599:Systole; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000378:metabolism*
D000959:Antihypertensive Agents; D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9