Abstract
Collagen metabolism in the extracellular matrix (ECM) is related to the pathogenesis of cardiovascular stiffness and remodeling in hypertension. We evaluated the association between collagen metabolism markers and the newly developed parameter, brachial-ankle pulse wave velocity (baPWV), in older hypertensive patients with left ventricular hypertrophy (LVH). We performed echocardiography and baPWV measurement using a new device, form PWV/ABI (Colin Medical Technology, Komaki, Japan), and measured plasma levels of markers of collagen metabolism such as procollagen type I C-terminal propeptide (PICP: a marker of collagen synthesis), collagen type I pyridinoline cross-linked C-terminal telopeptide (ICTP: a marker of collagen type I degradation), matrix metalloproteinase-1 (MMP-1: a marker of collagen degradation) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in 46 hypertensive patients with LVH. BaPWV was correlated with the plasma level of PICP (r=0.33, p=0.03) and ICTP (r=0.29, p=0.05) and the total TIMP-1/MMP-1 ratio (an index of collagen turnover; r=0.30, p=0.04). BaPWV was negatively correlated with the E/A ratio of left ventricular inflow (r=−0.36, p<0.05), while baPWV was not correlated with left ventricular mass index (LVMI; r=−0.175, p=0.25) or deceleration time of the mitral E wave (DCT; r=0.15, p=0.31). The measures of hypertensive heart disease, such as the E/A ratio, DCT or LVMI were not correlated with any collagen markers in this study. In multiple regression analysis adjusted for confounding factors such as age, sex, pulse pressure, mean blood pressure, pulse rate, LVMI, E/A ratio and DCT, the positive correlation between baPWV and total TIMP-1/MMP-1 ratio remained significant (p<0.05). In conclusion, arterial stiffness in high-risk older hypertensive patients may involve ECM collagen metabolism.
Similar content being viewed by others
Article PDF
References
Laurent S, Boutouyrie P, Asmar R, et al: Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension 2001; 37: 1236–1241.
Laurent S, Katsahian S, Fassot C, et al: Aortic stiffness is an independent predictor of fatal stroke in essential hypertension. Stroke 2003; 34: 1203–1206.
Blacher J, Asmar R, Djane S, London GM, Safar ME : Aortic pulse wave velocity as a marker of cardiovascular risk in hypertensive patients. Hypertension 1999; 33: 1111–1117.
Munakata M, Ito N, Nunokawa T, Yoshinaga K : Utility of automated brachial ankle pulse wave velocity measurements in hypertensive patients. Am J Hypertens 2003; 16: 653–657.
Yokoyama H, Aoki T, Imahori M, Kuramitsu M : Subclinical atherosclerosis is increased in type 2 diabetic patients with microalbuminuria evaluated by intima-media thickness and pulse wave velocity. Kidney Int 2004; 66: 448–454.
Munakata M, Sakuraba J, Tayama J, et al: Higher brachial-ankle pulse wave velocity is associated with more advanced carotid atherosclerosis in end-stage renal disease. Hypertens Res 2005; 28: 9–14.
Yamashina A, Tomiyama H, Arai T, et al: Brachial-ankle pulse wave velocity as a marker of atherosclerotic vascular damage and cardiovascular risk. Hypertens Res 2003; 26: 615–622.
Weber KT : Monitoring vascular sclerosis in hypertension: a new window of opportunity. Circulation 1998; 98: 498–500.
Shekhonin BV, Domogatsky SP, Muzykantov VR, Idelson GL, Rukosuev VS : Distribution of type I, III, IV and V collagen in normal and atherosclerotic human arterial wall: immunomorphological characteristics. Coll Relat Res 1985; 5: 355–368.
Lindsay MM, Maxwell P, Dunn FG : TIMP-1: a marker of left ventricular diastolic dysfunction and fibrosis in hypertension. Hypertension 2002; 40: 136–141.
Intengan HD, Schiffrin EL : Structure and mechanical properties of resistance arteries in hypertension: role of adhesion molecules and extracellular matrix determinants. Hypertension 2000; 36: 312–318.
Laviades C, Varo N, Fernandez J, et al: Abnormalities of the extracellular degradation of collagen type I in essential hypertension. Circulation 1998; 98: 535–540.
Tomiyama H, Koji Y, Yambe M, et al: Elevated C-reactive protein augments increased arterial stiffness in subjects with the metabolic syndrome. Hypertension 2005; 45: 997–1003.
Aso K, Miyata M, Kubo T, et al: Brachial-ankle pulse wave velocity is useful for evaluation of complications in type 2 diabetic patients. Hypertens Res 2003; 26: 807–813.
Kobayashi K, Akishita M, Yu W, Hashimoto M, Ohni M, Toba K : Interrelationship between non-invasive measurements of atherosclerosis: flow-mediated dilation of brachial artery, carotid intima-media thickness and pulse wave velocity. Atherosclerosis 2004; 173: 13–18.
Nakamura U, Iwase M, Nohara S, Kanai H, Ichikawa K, Iida M : Usefulness of brachial-ankle pulse wave velocity measurement: correlation with abdominal aortic calcification. Hypertens Res 2003; 26: 163–167.
Okamura T, Moriyama Y, Kadowaki T, Kanda H, Ueshima H : Non-invasive measurement of brachial-ankle pulse wave velocity is associated with serum C-reactive protein but not with α-tocopherol in Japanese middle-aged male workers. Hypertens Res 2004; 27: 173–180.
Takami T, Shigemasa M : Efficacy of various antihypertensive agents as evaluated by indices of vascular stiffness in elderly hypertensive patients. Hypertens Res 2003; 26: 609–614.
Tomiyama H, Arai T, Koji Y, et al: The age-related increase in arterial stiffness is augmented in phases according to the severity of hypertension. Hypertens Res 2004; 27: 465–470.
Yamashina A, Tomiyama H, Takeda K, et al: Validity, reproducibility, and clinical significance of noninvasive brachial-ankle pulse wave velocity measurement. Hypertens Res 2002; 25: 359–364.
Yambe M, Tomiyama H, Hirayama Y, et al: Arterial stiffening as a possible risk factor for both atherosclerosis and diastolic heart failure. Hypertens Res 2004; 27: 625–631.
Sahn DJ, DeMaria A, Kisslo J, Weyman A : Recommendations regarding quantitation in M-mode echocardiography: results of a survey of echocardiographic measurements. Circulation 1978; 58: 1072–1083.
Schiller NB, Shah PM, Crawford M, et al: Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr 1989; 2: 358–367.
Devereux RB, Reichek N : Echocardiographic determination of left ventricular mass in man. Anatomic validation of the method. Circulation 1977; 55: 613–618.
Devereux RB, Alonso DR, Lutas EM, et al: Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol 1986; 57: 450–458.
El Assaad MA, Topouchian JA, Darne BM, Asmar RG : Validation of the Omron HEM-907 device for blood pressure measurement. Blood Press Monit 2002; 7: 237–241.
Kohara K, Tabara Y, Tachibana R, Nakura J, Miki T : Microalbuminuria and arterial stiffness in a general population: the Shimanami Health Promoting Program (J-SHIPP) Study. Hypertens Res 2004; 27: 471–477.
Imanishi R, Seto S, Toda G, et al: High brachial-ankle pulse wave velocity is an independent predictor of the presence of coronary artery disease in men. Hypertens Res 2004; 27: 71–78.
Querejeta R, Lopez B, Gonzalez A, et al: Increased collagen type I synthesis in patients with heart failure of hypertensive origin: relation to myocardial fibrosis. Circulation 2004; 110: 1263–1268.
Hirono O, Fatema K, Nitobe J, et al: Long-term effects of benidipine hydrochloride on severe left ventricular hypertrophy and collagen metabolism in patients with essential hypertension. J Cardiol 2002; 39: 195–204.
Deschamps AM, Apple KA, Leonardi AH, et al: Myocardial interstitial matrix metalloproteinase activity is altered by mechanical changes in LV load: interaction with the angiotensin type 1 receptor. Circ Res 2005; 96: 1110–1118.
Ciulla MM, Paliotti R, Esposito A, et al: Different effects of antihypertensive therapies based on losartan or atenolol on ultrasound and biochemical markers of myocardial fibrosis: results of a randomized trial. Circulation 2004; 110: 552–557.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ishikawa, J., Kario, K., Matsui, Y. et al. Collagen Metabolism in Extracellular Matrix May Be Involved in Arterial Stiffness in Older Hypertensive Patients with Left Ventricular Hypertrophy. Hypertens Res 28, 995–1001 (2005). https://doi.org/10.1291/hypres.28.995
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1291/hypres.28.995
Keywords
This article is cited by
-
Harmine is an effective therapeutic small molecule for the treatment of cardiac hypertrophy
Acta Pharmacologica Sinica (2022)
-
Leukocyte matrix metalloproteinase and tissue inhibitor gene expression patterns in children with primary hypertension
Journal of Human Hypertension (2020)
-
Autophagy plays a critical role in Klotho gene deficiency-induced arterial stiffening and hypertension
Journal of Molecular Medicine (2019)
-
Circulating matrix metalloproteinases are associated with arterial stiffness in patients with type 1 diabetes: pooled analysis of three cohort studies
Cardiovascular Diabetology (2017)
-
Serum carboxy-terminal telopeptide of type I collagen (I-CTP) is predictive of clinical outcome in peripheral artery disease patients following endovascular therapy
Heart and Vessels (2017)