Shear stress and plaque destabilization

The influence of shear stress on plaque destabilization in carotid arteries

Investigators: Kim van der Heiden, Frank Gijsen, Ruoyu Xing, Jolanda Wentzel

Atherosclerosis is a lipid- and inflammation driven disease of the larger arteries and is found at specific locations in de vessel wall, i.e. at low and low, oscillary shear stress regions. This flow profile induces pro-inflammatory transcription factors like NF-kB [1] and AP-1 but reduces expression and/or activity of anti-inflammatory transcription factors such as KLF2 and Nrf2 [2], rendering the vascular wall vulnerable for atherosclerotic lesion development. Indeed, it was shown in ApoE -/- that introduction of a low or low, oscillatory shear stress pattern by placing a flow modifier around the carotid artery, generates plaques with characteristics of vulnerability in the low shear stress regions [3].


micro CTPlaque growth often leads to lumen narrowing, which results in a change in the shear stress distribution over the plaque [4]. Downstream of the plaque, shear stress is reduced and can be oscillatory, while upstream and at the plaque shoulders shear stress is elevated [4]. Evidence is accumulating that in the advanced state of the disease this increase in shear stress could negatively affect the stability of the plaque [4,5,6]. However, detailed information on the direct influence of high shear stress on plaque composition/stability is lacking.

To study the direct influence of high shear stress on plaque composition of advanced plaques in vivo, we will alter the flow, and thus shear stress, at pre-existing advanced plaques in the carotid artery of ApoE -/- and study plaque size and composition over time. Moreover, we will study the underlying molecular mechanisms involved in this process.

wss over time

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  2. Activation of Nrf2 in endothelial cells protects arteries from exhibiting a proinflammatory state. Zakkar M, Van der Heiden K, Luong le A, Chaudhury H, Cuhlmann S, Hamdulay SS, Krams R, Edirisinghe I, Rahman I, Carlsen H, Haskard DO, Mason JC, Evans PC, Arterioscler Thromb Vasc Biol. 2009 Nov;29(11):1851-7.
  3. Atherosclerotic lesion size and vulnerability are determined by patterns of fluid shear stress. Cheng C, Tempel D, van Haperen R, van der Baan A, Grosveld F, Deamen MJ, Krams R, de Crom R. Circulation. 2006 Jun 13;113(23):2744-53.
  4. Strain distribution over plaques in human coronary arteries relates to shear stress. Gijsen FJ, Wentzel JJ, Thury A, Mastik F, Schaar JA, Schuurbiers JC, Slager CJ, van der Giessen WJ, de Feyter PJ, van der Steen AF, Serruys PW. Am J Physiol Heart Circ Physiol. 2008 Oct;295(4):H1608-14
  5. The role of shear stress in the destabilization of vulnerable plaques and related therapeutic implications. Slager CJ, Wentzel JJ, Gijsen FJ, Thury A, van der Wal AC, Schaar JA, Serruys PW. Nat Clin Pract Cardiovasc Med. 2005 Sep;2(9):456-64
  6. High shear stress influences plaque vulnerability. Groen HC, Gijsen FJ, van der Lugt A, Ferguson MS, Hatsukami TS, Yuan C, van der Steen AF, Wentzel JJ, Neth Heart J. 2008 Aug;16(7-8):280-3