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Current Hypertension Reports

, Volume 13, Issue 3, pp 200–207 | Cite as

Vascular Mechanisms in the Pathogenesis of Stroke

  • Cristina Sierra
  • Antonio Coca
  • Ernesto L. Schiffrin
Article

Abstract

Stroke is one of the most devastating manifestations of two common diseases, atherosclerosis and hypertension. It represents the second leading cause of death and a major cause of disability worldwide. Besides age (a nonmodifiable risk factor), hypertension is the most important cardiovascular risk factor for developing both ischemic and hemorrhagic stroke, as well as small vessel disease predisposing to lacunar infarction, white matter lesions, and cerebral microbleeds. In addition, hypertension predisposes to atherosclerosis and cardiac diseases (notably atrial fibrillation), thereby promoting cerebral embolism. Inflammatory mechanisms play a central role in the pathogenesis and progression of atherosclerosis, plaque rupture, thrombosis, and stroke. Endothelial dysfunction, in part resulting from excessive production of reactive oxygen species, is an important mechanism of cerebrovascular damage. This article reviews recent data on vascular mechanisms that participate in the pathogenesis of stroke.

Keywords

Atherosclerosis Cerebral blood flow Hypertension Small vessel disease Cerebrovascular remodeling Aging Oxidative stress Endothelial dysfunction 

Notes

Disclosure

No potential conflicts of interest relevant to this article were reported.

References

Papers of particular interest, published recently, have been highlighted as • Of importance •• Of major importance

  1. 1.
    Di Carlo A. Human and economic burden of stroke. Age Ageing. 2009;38:4–5.PubMedCrossRefGoogle Scholar
  2. 2.
    Goldstein LB, Adams R, Alberts MJ, et al. Primary prevention of ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council: cosponsored by the Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group; Cardiovascular Nursing Council; Clinical Cardiology Council; Nutrition, Physical Activity, and Metabolism Council; and the Quality of Care and Outcomes Research Interdisciplinary Working Group: the American Academy of Neurology affirms the value of this guideline. Stroke. 2006;37:1583–633.PubMedGoogle Scholar
  3. 3.
    International Society of Hypertension Writing Group. International Society of Hypertension (ISH): statement on blood pressure lowering and stroke prevention. J Hypertens. 2003;21:651–63.CrossRefGoogle Scholar
  4. 4.
    Sierra C. Essential hypertension, cerebrovascular reactivity and risk of stroke. In: Yim PJ, editor. Vascular hemodynamics; bioengineering and clinical perspectives. Hoboken: Wiley-Blackwell; 2008. p. 299–314.Google Scholar
  5. 5.
    • McColl BW, Allan SM, Rothwell NJ. Systemic infection, inflammation and acute ischemic stroke. Neuroscience. 2009;158:1049–1061. This is a recent review about the role of infection in vascular inflammation as a trigger of acute stroke. PubMedCrossRefGoogle Scholar
  6. 6.
    •• Moskowitz MA, Lo EH, Iadecola C. The science of stroke: mechanisms in search of treatments. Neuron. 2010;67:181–198. This is a comprehensive review about the role of inflammation and atherosclerosis in the pathogenesis of stroke. PubMedCrossRefGoogle Scholar
  7. 7.
    Ungvari Z, Kaley G, Cabo R, et al. Mechanisms of vascular aging: new perspectives. J Gerontol A Biol Sci Med Sci. 2010;65:1028–41.PubMedCrossRefGoogle Scholar
  8. 8.
    •• Chrissobolis S, Faraci FM. The role of oxidative stress and NADPH oxidase in cerebrovascular disease. Trends Mol Med. 2008;14:495–501. This article provides a comprehensive explanation of the role of oxidative stress in cerebrovascular disease and a summary of studies performed by this scientific group. PubMedCrossRefGoogle Scholar
  9. 9.
    • Chen RL, Balami JS, Esiri MM, et al. Ischemic stroke in the elderly: an overview of evidence. Nat Rev Neurol. 2010;6:256–265. This is a broad review of cerebrovascular disease in the elderly. PubMedCrossRefGoogle Scholar
  10. 10.
    Breteler MMB, van Swieten JC, Bots ML, et al. Cerebral white matter lesions, vascular risk factors, and cognitive function in a population-based study: the Rotterdam Study. Neurology. 1994;44:1246–52.PubMedGoogle Scholar
  11. 11.
    Koton S, Schwammenthal Y, Merzeliak O, et al. Cerebral leukoaraiosis in patients with stroke or TIA: clinical correlates and 1-year outcome. Eur J Neurol. 2009;16:218–25.PubMedCrossRefGoogle Scholar
  12. 12.
    • Debette S, Markus HS.The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis. BMJ. 2010;341:c3666. This interesting paper systematically analyzes clinical evidence regarding WML. PubMedCrossRefGoogle Scholar
  13. 13.
    Farrall AJ, Wardlaw JM. Blood-brain barrier: ageing and microvascular disease—systematic review and meta-analysis. Neurobiol Aging. 2009;30:337–52.PubMedCrossRefGoogle Scholar
  14. 14.
    Drake CT, Iadecola C. The role of neuronal signalling in controlling cerebral blood flow. Brain Lang. 2007;102:141–52.PubMedCrossRefGoogle Scholar
  15. 15.
    Stoquart-ElSankari S, Baledent O, Gondry-Jouet C, et al. Aging effects on cerebral blood and cerebrospinal fluid flows. J Cereb Blood Flow Metab. 2007;27:1563–72.PubMedCrossRefGoogle Scholar
  16. 16.
    Love S, Miners S, Palmer J, et al. Insights into the pathogenesis and pathogenicity of cerebral amyloid angiopathy. Front Biosci. 2009;14:4778–92.PubMedCrossRefGoogle Scholar
  17. 17.
    Miller AA, Budzyn K, Sobey CG. Vascular dysfunction in cerebrovascular disease: mechanisms and therapeutic intervention. Clin Sci (Lond). 2010;119:1–17.CrossRefGoogle Scholar
  18. 18.
    Faraci FM, Heistad DD. Regulation of the cerebral circulation: role of endothelium and potassium channels. Physiol Rev. 1998;78:53–97.PubMedGoogle Scholar
  19. 19.
    Endemann DH, Schiffrin EL. Endothelial dysfunction. J Am Soc Nephrol. 2004;15:1983–92.PubMedCrossRefGoogle Scholar
  20. 20.
    Girouard H, Iadecola C. Neurovascular coupling in the normal brain and in hypertension, stroke, and Alzheimer disease. J Appl Physiol. 2006;100:328–35.PubMedCrossRefGoogle Scholar
  21. 21.
    Roquer J, Segura T, Serena J, Castillo J. Endothelial dysfunction, vascular disease and stroke: the ARTICO study. Cerebrovasc Dis. 2009;27 Suppl 1:25–37.PubMedCrossRefGoogle Scholar
  22. 22.
    Faraci FM. Reactive oxygen species: influence on cerebral vascular tone. J Appl Physiol. 2006;100:739–43.PubMedCrossRefGoogle Scholar
  23. 23.
    Pacher P, Beckman JS, Liaudet L. Nitric oxide and peroxynitrite in health and disease. Physiol Rev. 2007;87:315–424.PubMedCrossRefGoogle Scholar
  24. 24.
    Baumbach GL, Didion SP, Faraci FM. Hypertrophy of cerebral arterioles in mice deficient in expression of the gene for Cu/Zn superoxide dismutase. Stroke. 2006;37:1850–5.PubMedCrossRefGoogle Scholar
  25. 25.
    Baumbach GL, Sigmund CD, Faraci FM. Cerebral arteriolar structure in mice overexpressing human renin and angiotensinogen. Hypertension. 2003;41:50–5.PubMedCrossRefGoogle Scholar
  26. 26.
    Baumbach GL, Sigmund CD, Faraci FM. Structure of cerebral arterioles in mice deficient in expression of the gene for endothelial nitric oxide synthase. Circ Res. 2004;95:822–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Touyz RM, Schiffrin EL. Reactive oxygen species in vascular biology: implications in hypertension. Histochem Cell Biol. 2004;122:339–52.PubMedCrossRefGoogle Scholar
  28. 28.
    Marchesi C, Paradis P, Schiffrin EL. Role of the renin-angiotensin system in vascular inflammation. Trends Pharmacol Sci. 2008;29:367–74.PubMedCrossRefGoogle Scholar
  29. 29.
    • Elkind MSV. Inflammatory mechanisms of stroke. Stroke. 2010;41:S3–S8. This review summarizes the evidence about the association between hsCRP and stroke. PubMedCrossRefGoogle Scholar
  30. 30.
    Lawes CMM, Bennett DA, Feigin VL, Rodgers A. Blood pressure and stroke: an overview of published reviews. Stroke. 2004;35:776–85.PubMedCrossRefGoogle Scholar
  31. 31.
    Stamler J, Stamler R, Neaton JD. Blood pressure, systolic and diastolic, and cardiovascular risks. Arch Intern Med. 1993;153:598–615.PubMedCrossRefGoogle Scholar
  32. 32.
    Domanski MJ, Davis BR, Pfeffer MA, et al. Isolated systolic hypertension. Prognostic information provided by pulse pressure. Hypertension. 1999;34:375–80.PubMedGoogle Scholar
  33. 33.
    Laurent S, Katsahian S, Fassot C, et al. Aortic stiffness is an independent predictor of fatal stroke in essential hypertension. Stroke. 2003;34:1203–6.PubMedCrossRefGoogle Scholar
  34. 34.
    Kim CK, Lee SH, Kim BJ, et al. Age-independent association of pulse pressure with cerebral white matter lesions in asymptomatic elderly individuals. J Hypertens. 2011;29:325–9.PubMedCrossRefGoogle Scholar
  35. 35.
    •• Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol. 2010;9:689–701. This is the most complete review about cerebral WML with relation to pathogenesis and clinical characteristics. PubMedCrossRefGoogle Scholar
  36. 36.
    • Debette S, Beiser A, DeCarli C, et al. Association of MRI markers of vascular brain injury with incident stroke, mild cognitive impairment, dementia, and mortality. The Framingham Offspring Study. Stroke. 2010;41:600–606. This important study relates imaged vascular damage to the incidence of stroke, dementia, and mortality. PubMedCrossRefGoogle Scholar
  37. 37.
    • Knottnerus ILH, Govers-Riemslag JWP, Hamulyak K, et al. Endothelial activation in lacunar stroke subtypes. Stroke. 2010;41;1617–1622. This interesting study demonstrates differences in the fibrinolytic system, with increased levels of t-PA and reduced levels of PAI-1 that may be the result of endothelial activation leading to lacunar strokes.PubMedCrossRefGoogle Scholar
  38. 38.
    Hassan A, Markus HS. Genetics and ischaemic stroke. Brain. 2000;23:1784–812.CrossRefGoogle Scholar
  39. 39.
    Kiely DK, Wolf PA, Cupples LA, et al. Familial aggregation of stroke. The Framingham Study. Stroke. 1993;24:1366–71.PubMedGoogle Scholar
  40. 40.
    Brass LM, Isaacsohn JL, Merikangas KR, Robinette CD. A study of twins and stroke. Stroke. 1992;23:221–3.PubMedGoogle Scholar
  41. 41.
    Zafarmand MH, van der Schouw YT, Grobbee DE, et al. α-adducin Gly460Trp variant increases the risk of stroke in hypertensive dutch women. Hypertension. 2008;51:1665–70.PubMedCrossRefGoogle Scholar
  42. 42.
    van Rijn MJE, Bos MJ, Yazdanpanah M, et al. α-Adducin polymorphism, atherosclerosis, and cardiovascular and cerebrovascular risk. Stroke. 2006;37:2930–4.PubMedCrossRefGoogle Scholar
  43. 43.
    Morrison AC, Doris PA, Folsom AR, et al. G-protein β3 subunit and α-adducin polymorphisms and risk of subclinical and clinical stroke. Stroke. 2001;32:822–9.PubMedGoogle Scholar
  44. 44.
    Sharma P. Meta-analysis of the ACE gene in ischaemic stroke. J Neurol Neurosurg Psychiatry. 1998;64:227–30.PubMedCrossRefGoogle Scholar
  45. 45.
    Rubattu S, Stanzione R, Di Angelantonio E, et al. Atrial natriuretic peptide gene polymorphisms and risk of ischemic stroke in humans. Stroke. 2004;35:814–8.PubMedCrossRefGoogle Scholar
  46. 46.
    Kurl S, Ala-Kopsala M, Ruskoaho H, et al. Plasma N-terminal fragments of natriuretic peptides predict the risk of stroke and atrial fibrillation in men. Heart. 2009;95:1067–71.PubMedCrossRefGoogle Scholar
  47. 47.
    Carmelli D, DeCarli C, Swan GE, et al. Evidence for genetic variance in white matter hyperintensity volume in normal elderly male twins. Stroke. 1998;29:1177–81.PubMedGoogle Scholar
  48. 48.
    Sierra C, Coca A, Gómez-Angelats E, et al. Renin-angiotensin system genetic polymorphisms and cerebral white matter lesions in essential hypertension. Hypertension. 2002;39:343–7.PubMedCrossRefGoogle Scholar
  49. 49.
    • Paternoster L, Chen W, Sudlow CL. Genetic determinants of white matter hyperintensities on brain scans: a systematic assessment of 19 candidate gene polymorphisms in 46 studies in 19,000 subjects. Stroke. 2009;40:2020–2026. This is one of the few (and latest) reviews on the association of genetic factors and the development of cerebral WML. PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Cristina Sierra
    • 1
    • 2
  • Antonio Coca
    • 2
  • Ernesto L. Schiffrin
    • 1
  1. 1.Department of Medicine, Sir Mortimer B. Davis-Jewish General Hospital and Lady Davis Institute for Medical ResearchMcGill UniversityMontrealCanada
  2. 2.Hypertension Unit, Department of Internal Medicine, Institute of Medicine and Dermatology, Hospital Clinic (IDIBAPS)University of BarcelonaBarcelonaSpain

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