Inflammation and large arteries: Potential mechanisms for inflammation-induced arterial stiffness

Elsevier BV - Tập 6 - Trang 59-64 - 2012
Kaisa M. Mäki-Petäjä1, Ian B. Wilkinson1
1Clinical Pharmacology Unit, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK

Tóm tắt

Systemic inflammatory conditions are associated with an increased risk of cardiovascular disease (CVD). How exactly inflammation leads to this is not fully understood, but it has been suggested that arterial stiffening, could provide potential mechanisms to explain it. Chronic, systemic inflammatory conditions, as well as acute-models of inflammation are associated with arterial stiffening. Moreover, aortic stiffness can be reversed with successful immunomodulatory therapy. Although it seems evident that inflammation is involved in the process of aortic stiffening, the precise mechanism responsible for this remains unclear. There are number of possible mechanisms by which inflammation could lead to arterial stiffening. (1) Inflammation is associated with endothelial dysfunction and this can regulate arterial stiffness via changes in smooth muscle tone. (2) Inflammation leads to increased synthesis of matrix metalloproteinases, which can degrade elastin, resulting in stiffening. (3) Several mediators of inflammation may directly stimulate vascular calcification, whereas endogenous inhibitors of vascular calcification are downregulated during inflammation, both of which can lead to stiffening. (4) During inflammation arterial glycosaminoglycan (GAG) synthesis is upregulated. In animal models, an overproduction of certain GAGs in the aorta results in stiffening of the arterial wall by thinning of elastic lamellae. (5) Finally, direct vascular inflammation could lead to arterial stiffening by changing the composition of extracellular matrix. This review aims to discuss potential mechanisms by which inflammation could lead to aortic stiffening.

Tài liệu tham khảo

Boutouyrie P, Tropeano AI, Asmar R, Gautier I, Benetos A, Lacolley P, et al. Aortic stiffness is an independent predictor of primary coronary events in hypertensive patients: a longitudinal study. Hypertension 2002 January;39:10–5.

Cruickshank K, Riste L, Anderson SG, Wright JS, Dunn G, Gosling RG. Aortic pulse-wave velocity and its relationship to mortality in diabetes and glucose intolerance: an integrated index of vascular function? Circulation 2002 October 15;106: 2085–90.

Mattace-Raso FU, van der Cammen TJ, Hofman A, van Popele NM, Bos ML, Schalekamp MA, et al. Arterial stiffness and risk of coronary heart disease and stroke: the Rotterdam Study. Circulation 2006 February 7;113:657–63.

Pasceri V, Yeh ET. A tale of two diseases: atherosclerosis and rheumatoid arthritis. Circulation 1999 November 23;100: 2124–6.

Angel K, Provan SA, Gulseth HL, Mowinckel P, Kvien TK, Atar D. Tumor necrosis factor-alpha antagonists improve aortic stiffness in patients with inflammatory arthropathies: a controlled study. Hypertension 2010 February;55:333–8.

Xu J, Xie Z, Reece R, Pimental D, Zou MH. Uncoupling of endothelial nitric oxidase synthase by hypochlorous acid: role of NAD(P)H oxidase-derived superoxide and peroxynitrite. Arterioscler Thromb Vasc Biol 2006 December;26:2688–95.

Rabelink TJ, Luscher TF. Endothelial nitric oxide synthase: host defense enzyme of the endothelium? Arterioscler Thromb Vasc Biol 2006 February;26:267–71.

Laursen JB, Somers M, Kurz S, McCann L, Warnholtz A, Freeman BA, et al. Endothelial regulation of vasomotion in apoE-deficient mice: implications for interactions between peroxynitrite and tetrahydrobiopterin. Circulation 2001 March 6;103:1282–8.

Kuzkaya N, Weissmann N, Harrison DG, Dikalov S. Interactions of peroxynitrite, tetrahydrobiopterin, ascorbic acid, and thiols: implications for uncoupling endothelial nitric-oxide synthase. J Biol Chem 2003 June 20;278:22,546–22,554.

Wallberg-Jonsson S, Cvetkovic JT, Sundqvist KG, Lefvert AK, Rantapaa-Dahlqvist S. Activation of the immune system and inflammatory activity in relation to markers of athero-thrombotic disease and atherosclerosis in rheumatoid arthritis. J Rheumatol 2002 May;29:875–82.

Savage CO, Pottinger BE, Gaskin G, Pusey CD, Pearson JD. Auto-antibodies developing to myeloperoxidase and proteinase 3 in systemic vasculitis stimulate neutrophil cytotoxicity toward culturedendothelial cells.Am J Pathol 1992 August;141:335–42.

Montero I, Orbe J, Varo N, Beloqui O, Monreal JI, Rodriguez 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 April 4; 47:1369–78.

Yasmin, Wallace S, McEniery CM, Dakham Z, Pusalkar P, Maki-Petaja K, Ashby MJ, et al. Matrix metalloproteinase-9 (MMP-9), MMP-2, and serum elastase activity are associated with systolic hypertension and arterial stiffness. Arterioscler Thromb Vasc Biol 2005 February;25:372.

Rheumatoid vasculitis. Johns Hopkins Vasculitis Centre, http://vasculitis.med.jhu.edu/types/rheumatoid.html; 2007. Ref type: internet communication.

Watts RA, Carruthers DM, Symmons DP, Scott DG. The incidence of rheumatoid vasculitis in the Norwich Health Authority. Br J Rheumatol 1994 September;33: 832–3.