Abstract
Osteopontin (OPN) has recently emerged as a key factor in both vascular remodelling and development of atherosclerosis. It has been reported that OPN is regulated by the renin–angiotensin–aldosterone system (RAAS). The aim of this study was to clarify the effect of angiotensin II receptor blockade with valsartan on plasma OPN levels in patients with essential hypertension (EHT). Forty-six patients (mean age, 64±11 years) with EHT were randomly assigned to treatment with amlodipine or valsartan. There were no significant differences in baseline clinical characteristics between the two groups. Blood sampling and blood pressure evaluation were performed before and after 24 weeks of treatment. After 24 weeks, both systolic blood pressure (SBP) and diastolic blood pressure (DBP) were decreased significantly and by the same degree in each treatment group. However, valsartan but not amlodipine decreased plasma OPN levels (baseline and 24-week data—valsartan: 614±224 ng ml−1, 472±268 ng ml−1, P=0.006; amlodipine: 680±151 ng ml−1, 687±234 ng ml−1, P>0.999). A positive correlation between the reduction in OPN and the log natural (ln) C-reactive protein (CRP) was seen in the valsartan-treated group. Stepwise regression analysis showed that treatment with valsartan and the reduction of ln CRP were associated with the reduction in OPN levels, and this association was independent of the reduction in SBP or aldosterone levels (valsartan: β=0.332, P=0.026; ln CRP reduction: β=0.366, P=0.015). These results suggest that suppression of the RAAS and inflammation may decrease plasma OPN levels.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 digital issues and online access to articles
$119.00 per year
only $9.92 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Junaid A, Amara FM . Osteopontin: correlation with interstitial fibrosis in human diabetic kidney and PI3-kinase-mediated enhancement of expression by glucose in human proximal tubular epithelial cells. Histopathology 2004; 44: 136–146.
Liaw L, Almeida M, Hart CE, Schwartz SM, Giachelli CM . Osteopontin promotes vascular cell adhesion and spreading and is chemotactic for smooth muscle cells in vitro. Circ Res 1994; 74: 214–224.
Liaw L, Lindner V, Schwartz SM, Chambers AF, Giachelli CM . Osteopontin and beta sub integrin are coordinately expressed in regenerating endothelium in vivo and stimulate Arg-Gly-Asp-dependent endothelial migration in vitro. Circ Res 1995; 77: 665–672.
Liaw L, Skinner MP, Raines EW, Ross R, Cheresh DA, Schwartz SM et al. The adhesive and migratory effects of osteopontin are mediated via distinct cell surface integrins. Role of alpha v beta 3 in smooth muscle cell migration to osteopontin in vitro. J Clin Invest 1995; 95: 713–724.
Malyankar UM, Scatena M, Suchland KL, Yun TJ, Clark EA, Giachelli CM . Osteoprotegerin is an alpha vbeta 3-induced, NF-kappa B-dependent survival factor for endothelial cells. J Biol Chem 2000; 275: 20959–20962.
Mazzali M, Kipari T, Ophascharoensuk V, Wesson JA, Johnson R, Hughes J . Osteopontin—a molecule for all seasons. QJM 2002; 95: 3–13.
Campos AH, Zhao Y, Pollman MJ, Gibbons GH . DNA microarray profiling to identify angiotensin-responsive genes in vascular smooth muscle cells: potential mediators of vascular disease. Circ Res 2003; 92: 111–118.
Irita J, Okura T, Kurata M, Miyoshi K, Fukuoka T, Higaki J . Osteopontin in rat renal fibroblasts: functional properties and transcriptional regulation by aldosterone. Hypertension 2008; 51: 507–513.
Bruemmer D, Collins AR, Noh G, Wang W, Territo M, Arias-Magallona S et al. Angiotensin II-accelerated atherosclerosis and aneurysm formation is attenuated in osteopontin-deficient mice. J Clin Invest 2003; 112: 1318–1331.
Minoretti P, Falcone C, Calcagnino M, Emanuele E, Buzzi MP, Coen E et al. Prognostic significance of plasma osteopontin levels in patients with chronic stable angina. Eur Heart J 2006; 27: 802–807.
Kurata M, Okura T, Watanabe S, Fukuoka T, Higaki J . Osteopontin and carotid atherosclerosis in patients with essential hypertension. Clin Sci 2006; 111: 319–324.
Naito M, Shenoy A, Aoyama I, Koopmeiners JS, Komers R, Schnaper HW et al. High ambient glucose augments angiotensin II-induced proinflammatory gene mRNA expression in human mesangial cells: effects of valsartan and simvastatin. Am J Nephrol 2009; 30: 99–111.
Cianchetti S, Del Fiorentino A, Colognato R, Di Stefano R, Franzoni F, Pedrinelli R . Anti-inflammatory and anti-oxidant properties of telmisartan in cultured human umbilical vein endothelial cells. Atherosclerosis 2008; 198: 22–28.
Takai S, Kim S, Sakonjo H, Miyazaki M . Mechanisms of angiotensin II type 1 receptor blocker for anti-atherosclerotic effect in monkeys fed a high-cholesterol diet. J Hypertens 2003; 21: 361–369.
Fujiwara Y, Shiraya S, Miyake T, Yamakawa S, Aoki M, Makino H et al. Inhibition of experimental abdominal aortic aneurysm in a rat model by the angiotensin receptor blocker valsartan. Int J Mol Med 2008; 22: 703–708.
Manabe S, Okura T, Watanabe S, Fukuoka T, Higaki J . Effects of angiotensin II receptor blockade with valsartan on pro-inflammatory cytokines in patients with essential hypertension. J Cardiovasc Pharmacol 2005; 46: 735–739.
Okura T, Watanabe S, Kurata M, Koresawa M, Irita J, Enomoto D et al. Long-term effects of angiotensin II receptor blockade with valsartan on carotid arterial stiffness and hemodynamic alterations in patients with essential hypertension. Clin Exp Hypertens 2008; 30: 415–422.
Abe K, Nakashima H, Ishida M, Miho N, Sawano M, Soe NN et al. Angiotensin II-induced osteopontin expression in vascular smooth muscle cells involves Gq/11, Ras, ERK, Src and Ets-1. Hypertens Res 2008; 31: 987–998.
Kramer AB, van der Meulen EF, Hamming I, van Goor H, Navis G . Effect of combining ACE inhibition with aldosterone blockade on proteinuria and renal damage in experimental nephrosis. Kidney Int 2007; 71: 417–424.
Navalkar S, Parthasarathy S, Santanam N, Khan BV . Irbesartan, an angiotensin type 1 receptor inhibitor, regulates markers of inflammation in patients with premature atherosclerosis. J Am Coll Cardiol 2001; 37: 440–444.
Kurata M, Okura T, Irita J, Enomoto D, Nagao T, Jotoku M et al. The relationship between osteopontin and adiponectin in patients with essential hypertension. Clin Exp Hypertens 2010 (in press).
Tanaka N, Momiyama Y, Ohmori R, Yonemura A, Ayaori M, Ogura M et al. Effect of atorvastatin on plasma osteopontin levels in patients with hypercholesterolemia. Arterioscler Thromb Vasc Biol 2006; 26: e129–e130.
Montero I, Orbe J, Varo N, Beloqui O, Monreal JI, Rodríguez JA et al. C-reactive protein induces matrix metalloproteinase-1 and -10 in human endothelial cells: implications for clinical and subclinical atherosclerosis. J Am Coll Cardiol 2006; 47: 1369–1378.
Kurokawa M, Konno S, Matsukura S, Kawaguchi M, Ieki K, Suzuki S et al. Effects of corticosteroids on osteopontin expression in a murine model of allergic asthma. Int Arch Allergy Immunol 2009; 149 (Suppl 1): 7–13.
Mochizuki S, Dahlöf B, Shimizu M, Ikewaki K, Yoshikawa M, Taniguchi I et al. Valsartan in a Japanese population with hypertension and other cardiovascular disease (Jikei Heart Study): a randomised, open-label, blinded endpoint morbidity-mortality study. Lancet 2007; 369: 1431–1439.
Sawada T, Yamada H, Dahlof B, Matsubara H . Effects of valsartan on morbidity and mortality in uncontrolled hypertensive patients with high cardiovascular risks: KYOTO HEART Study. Eur Heart J 2009; 30: 2461–2469.
Sodhi CP, Phadke SA, Batlle D, Sahai A . Hypoxia stimulates osteopontin expression and proliferation of cultured vascular smooth muscle cells. Diabetes 2001; 50: 1482–1490.
Wang X, Louden C, Ohlstein EH, Stadel JM, Gu J-L, Yue T-L . Osteopontin expression in platelet-derived growth factor-stimulated vascular smooth muscle cells and carotid artery after balloon angioplasty. Arterioscler Thromb Vasc Biol 1996; 16: 1365–1372.
Giachelli CM, Bae N, Almeida M, Denhardt DT, Alpers CE, Schwartz SM . Osteopontin is elevated during neointima formation in rat arteries and is a novel component of human atherosclerotic plaques. J Clin Invest 1993; 92: 1686–1696.
Endlich N, Sunohara M, Nietfeld W, Wolski EW, Schiwek D, Kränzlin B et al. Analysis of differential gene expression in stretched podocytes: osteopontin enhances adaptation of podocytes to mechanical stress. FASEB J 2002; 16: 1850–1852.
Cecilia M, Giachelli SMS, Liaw L . Molecular and cellular biology of osteopontin potential role in cardiovascular disease. Trends Cardiovasc Med 1995; 5: 88–95.
Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto Jr AM, Kastelein JJ et al. Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective study of the JUPITER trial. Lancet 2009; 373: 1175–1182.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no conflict of interest.
Rights and permissions
About this article
Cite this article
Kurata, M., Okura, T., Irita, J. et al. Angiotensin II receptor blockade with valsartan decreases plasma osteopontin levels in patients with essential hypertension. J Hum Hypertens 25, 334–339 (2011). https://doi.org/10.1038/jhh.2010.73
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/jhh.2010.73
Keywords
This article is cited by
-
Possible role of LCZ696 in atherosclerosis: new inroads and perspective
Molecular and Cellular Biochemistry (2023)
-
Plasma thrombin-cleaved osteopontin elevation after carotid artery stenting in symptomatic ischemic stroke patients
Hypertension Research (2012)