Linking peripheral atherosclerosis to blood–brain barrier disruption: elucidating its role as a manifestation of cerebral small vessel disease in vascular cognitive impairment

Ádám Nyúl-Tóth, Roland Patai, Anna Csiszar, Anna Ungvari*, Rafal Gulej, Peter Mukli, Andriy Yabluchanskiy, Zoltan Benyo, Peter Sotonyi, Calin I. Prodan, Eric M. Liotta, Peter Toth, Fanny Elahi, Péter Barsi, Pál Maurovich-Horvat, Farzaneh A. Sorond, Stefano Tarantini, Zoltan Ungvari

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

12 Scopus citations

Abstract

Aging plays a pivotal role in the pathogenesis of cerebral small vessel disease (CSVD), contributing to the onset and progression of vascular cognitive impairment and dementia (VCID). In older adults, CSVD often leads to significant pathological outcomes, including blood–brain barrier (BBB) disruption, which in turn triggers neuroinflammation and white matter damage. This damage is frequently observed as white matter hyperintensities (WMHs) in neuroimaging studies. There is mounting evidence that older adults with atherosclerotic vascular diseases, such as peripheral artery disease, ischemic heart disease, and carotid artery stenosis, face a heightened risk of developing CSVD and VCID. This review explores the complex relationship between peripheral atherosclerosis, the pathogenesis of CSVD, and BBB disruption. It explores the continuum of vascular aging, emphasizing the shared pathomechanisms that underlie atherosclerosis in large arteries and BBB disruption in the cerebral microcirculation, exacerbating both CSVD and VCID. By reviewing current evidence, this paper discusses the impact of endothelial dysfunction, cellular senescence, inflammation, and oxidative stress on vascular and neurovascular health. This review aims to enhance understanding of these complex interactions and advocate for integrated approaches to manage vascular health, thereby mitigating the risk and progression of CSVD and VCID.

Original languageEnglish (US)
Pages (from-to)6511-6536
Number of pages26
JournalGeroScience
Volume46
Issue number6
DOIs
StatePublished - Dec 2024

Funding

Open access funding provided by Semmelweis University. This work was supported by grants from the American Heart Association (RG: AHA916225, ANT: AHA834339, and ST: AHA CDA941290), the Oklahoma Center for the Advancement of Science and Technology, the National Institute on Aging (RF1AG072295, R01AG055395, R01AG068295, R01AG070915, K01AG073614, K01AG073613, and R03AG070479), the National Institute of Neurological Disorders and Stroke (R01NS100782), the National Cancer Institute (R01CA255840), the Oklahoma Shared Clinical and Translational Resources (U54GM104938) with an Institutional Development Award (IDeA) from NIGMS, the Presbyterian Health Foundation, the Reynolds Foundation, the Oklahoma Nathan Shock Center (P30AG050911), and the Cellular and Molecular GeroScience CoBRE (P20GM125528), the NCI Cancer Center Support Grant (P30 CA225520) and the Oklahoma Tobacco Settlement Endowment Trust. ANT and AU were supported by TKP2021-NKTA-47, implemented with the support provided by the Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund, financed under the TKP2021-NKTA funding scheme; by funding through the National Cardiovascular Laboratory Program (RRF-2.3.1\u201321-2022\u201300003) provided by the Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund; Project no. 135784 implemented with the support provided from the National Research, Development and Innovation Fund of Hungary, financed under the K20 funding scheme and the European University for Well-Being (EUniWell) program (grant agreement number: 101004093/EUniWell/EAC-A02-2019/EAC-A02-2019\u20131). The 4.0 version of ChatGPT, developed by OpenAI, was used as a language tool to refine our writing, enhancing the clarity of our work.

Keywords

  • Aging
  • Arteriosclerosis
  • Atherogenesis
  • Atherosclerosis
  • Cerebral circulation
  • Cerebromicrovascular
  • Large vessel disease
  • Leukoaraiosis
  • Peripheral artery disease
  • Senescence
  • White matter hyperintensities
  • White matter injury

ASJC Scopus subject areas

  • Aging
  • veterinary (miscalleneous)
  • Complementary and alternative medicine
  • Geriatrics and Gerontology
  • Cardiology and Cardiovascular Medicine

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