Tissue inhibitor of metalloproteinase-1 and matrix metalloproteinase-9 levels in patients with hypertension

Relationship to tissue Doppler indices of diastolic relaxation

Muzahir H. Tayebjee, Sunil K. Nadar, Robert J. MacFadyen, Gregory Y H Lip

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

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. 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. 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). 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.

Original languageEnglish
Pages (from-to)770-774
Number of pages5
JournalAmerican Journal of Hypertension
Volume17
Issue number9
DOIs
Publication statusPublished - Sep 2004

Fingerprint

Tissue Inhibitor of Metalloproteinase-1
Matrix Metalloproteinase 9
Hypertension
Matrix Metalloproteinase Inhibitors
Diastolic Heart Failure
Left Ventricular Dysfunction
Left Ventricular Hypertrophy
Collagen Type I
Matrix Metalloproteinases
Extracellular Matrix
Heart Diseases
Fibrosis
Enzyme-Linked Immunosorbent Assay
Weights and Measures

Keywords

  • echocardiography
  • Extracellular matrix
  • hypertension
  • matrix metalloproteinase-9
  • tissue Doppler
  • tissue inhibitor of metalloproteinase-1

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Tissue inhibitor of metalloproteinase-1 and matrix metalloproteinase-9 levels in patients with hypertension : Relationship to tissue Doppler indices of diastolic relaxation. / Tayebjee, Muzahir H.; Nadar, Sunil K.; MacFadyen, Robert J.; Lip, Gregory Y H.

In: American Journal of Hypertension, Vol. 17, No. 9, 09.2004, p. 770-774.

Research output: Contribution to journalArticle

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N2 - 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. 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. 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). 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.

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