Markers of collagen synthesis is related to blood pressure and vascular hypertrophy: a LIFE substudy

Olsen, Michael Hecht; Christensen, Mette Krogh; Wachtell, Kristian; Tuxen, Christian; Fossum, Eigil; Bang, Lia E.; Wiinberg, Niels; Devereux, Richard B.; Kjeldsen, Sverre E.; Hildebrandt, Per; Dige‐Petersen, Harriet; Rokkedal, Jens; Ibsen, Hans

doi:10.1038/sj.jhh.1001819

Cited by 32 publications

(21 citation statements)

References 26 publications

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“…Apart from 1 report detailing elevated plasma levels of CITP in subjects with untreated hypertensive compared with normotensive subjects, 16 most clinical studies associate hypertension with diminished CITP and MMP activity [17][18][19] and greater vessel type I collagen content. 20 Nonetheless, based on the in vivo results presented here and our previous ex vivo findings, 3 it appears that MMPs are induced within days of the onset of hypertensive conditions and participate in collagen breakdown, increasing vessel distensibility.…”

Section: Discussionmentioning

confidence: 99%

Role of Matrix Metalloproteinases in Early Hypertensive Vascular Remodeling

Flamant

Placier²,

Dubroca³

et al. 2007

Hypertension

158

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Abstract-Hypertension is associated with vascular remodeling characterized by rearrangement of extracellular matrix proteins. To evaluate how matrix metalloproteinase (MMP)-9 contributes to the progression of hypertensive vascular disease in vivo, wild-type (wt) or MMP-9 Ϫ/Ϫ mice were treated with angiotensin II (Ang II; 1 g/kg per minute, by minipump) plus a 5% NaCl diet during 10 days. Baseline blood pressure was equivalent in wt and knockout mice, but Ang II treatment increased systolic blood pressure to a greater extent (PϽ0.05) in MMP-9 Ϫ/Ϫ mice (94Ϯ6 to 134Ϯ6 mm Hg; PϽ0.001) than in wt animals (93Ϯ4 to 114Ϯ6 mm Hg; PϽ0.01). In wt mice, Ang II treatment increased the carotid artery pressure-diameter relationship significantly, and maximal diameter reached 981Ϯ19 m (PϽ0.01 versus sham; 891Ϯ10 m). In contrast, in MMP-9 Ϫ/Ϫ mice, carotid artery compliance was actually reduced after Ang II (PϽ0.05), and maximal diameter only reached 878Ϯ13 m. Ang II treatment induced MMP-2 and increased carotid media thickness equally in both phenotypes. However, MMP-9 induction and in situ gelatinase activity were only enhanced in Ang II-treated wt mice, and vessels from these mice also produced more collagen I breakdown products than their MMP-9 Ϫ/Ϫ counterparts (PϽ0.05). Inversely, staining for collagen IV was particularly enhanced in vessels from MMP-9 Ϫ/Ϫ mice treated with Ang II. These results demonstrate the following: (1) the onset of Ang II-induced hypertension is accompanied by increased MMP-9 activity in conductance vessels; (2) absence of MMP-9 activity results in vessel stiffness and increased pulse pressure; and (3) MMP-9 activation is associated with a beneficial role early on in hypertension by preserving vessel compliance and alleviating blood pressure increase. Key Words: angiotensin Ⅲ metalloproteinases Ⅲ remodeling Ⅲ hypertension Ⅲ collagen B lood pressure is a major determinant of vessel wall structure and composition. Any change in strain will generate counteracting radial and tangential forces that drive transformations in the vessel wall to accommodate the new pressure setting and restore basal levels of tensile stress. 1 It therefore follows that a key characteristic of hypertensive conductance arteries is increased wall thickness accompanied by enhanced rigidity. In hypertensive patients, this is manifest by elevated pulse wave velocity, an independent predictor of mortality in patients with end-stage renal failure, hypertension, and diabetes, as well as in older individuals. 2 Nevertheless, using an ex vivo model of carotid artery, we have shown recently that early vascular remodeling in the hypertensive context is actually associated with increased conductance vessel distensibility rather than rigidity. 3 In fact, results from our own laboratory 3 and others 4 -8 have shown that exposing arteries or vascular cells to stretch induces the release of matrix metalloproteinases (MMPs). This perplexing observation led us to hypothesize that increased compliance may be an early compensatory mechanism allowi...

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Section: Discussionmentioning

confidence: 99%

Role of Matrix Metalloproteinases in Early Hypertensive Vascular Remodeling

Flamant

Placier²,

Dubroca³

et al. 2007

Hypertension

158

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“…We did not measure other markers of collagen synthesis (type I carboxy-terminal pro-collagen peptide) or degradation (type I collagen carboxy-terminal telopeptide) that may have been related to echocardiographic measures. 43,44 Additionally, we did not assess genetic factors, which may have explained some of the variation in PIIINP levels. Lastly, transmitral and tissue Doppler measurements were not available at this examination.…”

Section: Study Limitationsmentioning

confidence: 99%

Clinical and echocardiographic correlates of plasma procollagen type III amino-terminal peptide levels in the community

Wang

Larson

Benjamin

et al. 2007

American Heart Journal

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Background-Left ventricular remodeling is characterized by increased collagen deposition in the extracellular matrix. Levels of plasma pro-collagen type III amino-terminal peptide (PIIINP), a marker of collagen turnover, are elevated in the setting of recent myocardial infarction, heart failure, and cardiomyopathy. Whether plasma PIIINP levels are a useful indicator of subclinical left ventricular abnormalities in ambulatory individuals has not been studied.

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“…17 However, several studies have shown that serum markers of collagen turnover are useful in the diagnosis of myocardial fibrosis, especially serum procollagen type I propeptide (PIP), which is significantly higher in hypertensive patients with LVH than in normotensive controls. [18][19][20] It also correlates with collagen volume fraction (CVF) on endomyocardial biopsies and decreases in parallel with its regression during antihypertensive treatment. 19,21 Moreover, transforming growth factor (TGF)-β1 is known to play an important role in myocardial fibrosis by stimulating the synthesis of matrix molecules in hypertensive heart disease.…”

mentioning

confidence: 99%

“…In the present study, we compared target organ status, such as LVH, parameters of LV diastolic function, and biochemical markers of myocardial fibrosis (concentrations of TGF-β1 and PIP) [17][18][19][20][21][22][23][24][25]27 in individuals with NT, WCH, and EH. We also ascertained the correlation between the biochemical markers of myocardial fibrosis and indices of LV diastolic function in patients with WCH.…”

mentioning

confidence: 99%

Target Organ Status in White-Coat Hypertensives Usefulness of Serum Procollagen Type I Propeptide in the Respect of Left Ventricular Diastolic Dysfunction

Ihm

Youn

Park

et al. 2009

Circ J

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Background Myocardial fibrosis is a feature of diastolic dysfunction and target organ damage, which was compared among subjects with normotension (NT), white-coat hypertension (WCH) and essential hypertension (EH). Serum procollagen type I propeptide (PIP) level was assessed as a marker of diastolic dysfunction in WCH. Methods and ResultsOf 90 subjects, 30 had NT and 30 had WCH (ambulatory daytime blood pressure <135/85 mmHg) and 30 had EH (untreated mild to moderate hypertension); all underwent biochemical and echocardiographic examinations. Those with WCH had a lower left ventricular (LV) mass index than those with EH, but it was higher than in the NT group. WCH patients had a lower mitral valve E/A ratio and a higher LV E/E' (E': septal mitral annular peak velocity) ratio than NT patients, whereas these values were higher and lower respectively than in the EH group. The LV E/E' ratio, an estimate of LV diastolic function, correlated with the serum PIP concentration in WCH patients (r=0.39, P=0.03). Conclusion WCH is an intermediate group between NT and EH in respect of target organ damage. These results show a relationship between LV diastolic function and serum PIP in WCH, so the serum PIP level may be a useful marker of diastolic dysfunction and target organ damage in such patients. (Circ J 2009; 73: 100 -105)

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Markers of collagen synthesis is related to blood pressure and vascular hypertrophy: a LIFE substudy

Cited by 32 publications

References 26 publications

Role of Matrix Metalloproteinases in Early Hypertensive Vascular Remodeling

Role of Matrix Metalloproteinases in Early Hypertensive Vascular Remodeling

Clinical and echocardiographic correlates of plasma procollagen type III amino-terminal peptide levels in the community

Target Organ Status in White-Coat Hypertensives Usefulness of Serum Procollagen Type I Propeptide in the Respect of Left Ventricular Diastolic Dysfunction

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