Table 3.

Representative clinical studies demonstrating the relationship between MMP or TIMP levels and hypertension

Study Year Type	Subjects	Design	Findings	Ref
1998 Clinical Trial	37 patients with essential hypertension, 23 control normotensive subjects	Measure serum levels of carboxy-terminal telopeptide of collagen type I (marker of collagen degradation), MMP-1, TIMP-1, and MMP-1/TIMP-1 ratio. Repeat measurements after 1 year treatment with the ACE inhibitor lisinopril	No difference in collagen type I levels. Decreased MMP-1 and increased TIMP-1 in hypertensive versus normotensive subjects. Hypertensive patients with left ventricular hypertrophy showed lower free MMP-1 and collagen type I and higher free TIMP-1 than hypertensive patients without left ventricular hypertrophy. Patients treated with lisinopril showed increased serum collagen type I and free MMP-1 and decreased free TIMP-1	327
2003 Clinical Trial	42 hypertensive patients	6 Months treatment with amlodipine	Normalized plasma levels of MMP-9, but not MMP-2	328
2006 Cross Sectional	44 hypertensive patients, 44 controls	Measure plasma levels of MMP-2, MMP-9, and TIMP-1	Higher plasma levels of MMP-2, MMP-9, and TIMP-1 in hypertensive versus control subjects	329
2007 Cross Sectional	202 hypertensive patients, 54 control	Measure carotid-femoral and carotid-radial pulse wave velocity to determine arterial elasticity. Measure serum levels of MMP-9 and TIMP-1 levels by ELISA	Higher serum levels of MMP-9 and TIMP-1 in hypertensive patients versus control subjects. Age, systolic blood pressure, heart rate and TIMP-1 levels were independent predictors of carotid-femoral pulse wave velocity in hypertensive subjects	330
2009 Clinical Trial	33 patients with stage 1 hypertension, 16 age-matched control	Assess serum levels of MMP-9 and TIMP-1 in the hypertensive group before and after 3-month-anti-hypertensive therapy	Pre-treatment serum MMP-9 levels were higher and TIMP-1 levels were lower in hypertensive group versus control. Anti-hypertensive treatment was associated with decreased serum MMP-9 levels and increased TIMP-1 levels	221
2009 Randomized Clinical Trial	595 Non-hypertensive Framingham Offspring Study, participants without prior heart failure or myocardial infarction, mean age 55 years, (360 women)	Measure plasma levels of MMP-9, TIMP-1, and procollagen III N-terminal peptide for 4 years	81 Subjects (51 women) developed hypertension, and 198 (114 women) progressed to higher blood pressure. Subjects with detectable MMP-9 had 1.97-fold higher risk of blood pressure progression than those with undetectable MMP-9. A 1-SD increment of log-TIMP-1 was associated with 50% higher incidence of hypertension and 21% higher risk of blood pressure progression. Individuals in the top TIMP-1 tertile had a 2.15-fold increased risk of hypertension and 1.68-fold increased risk of blood pressure progression relative to the lowest tertile. Plasma procollagen III N-terminal peptide was not associated with hypertension or blood pressure progression.	331
2010 Cross sectional	64 Children (34 males, 30 females)	Measure circulating levels of MMP-2, MMP-9, TIMP-2, insulin-like growth factor-I and insulin growth factor binding protein-3	Circulating levels of MMP-2 and MMP-9 correlate with systolic blood pressure and vascular function. MMP-2 was an independent predictor of systolic blood pressure. MMP-9 was an independent predictor of vascular dysfunction	332