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Padarti et al. Vessel Plus 2018;2:21 Vessel Plus
DOI: 10.20517/2574-1209.2018.34

Review Open Access

Recent advances in cerebral cavernous
malformation research

Akhil Padarti, Jun Zhang

Department of Biomedical Sciences, Texas Tech University Health Science Center El Paso, El Paso, TX 79905, USA.
Correspondence to: Dr. Jun Zhang, Department of Biomedical Sciences, Texas Tech Udniversity Health Science Center, 5001 El
Paso Drive, El Paso, El Paso, TX 79905, USA. E-mail: jun.zhang2000@gmail.com

How to cite this article: Padarti A, Zhang J. Recent advances in cerebral cavernous malformation research. Vessel Plus 2018;2:21.
http://dx.doi.org/10.20517/2574-1209.2018.34

Received: 15 May 2018 First Decision: 23 Jul 2018 Revised: 1 Aug 2018 Accepted: 15 Aug 2018 Published: 28 Aug 2018
Science Editor: Aaron S. Dumont Copy Editor: Huan-Liang Wu Production Editor: Cai-Hong Wang

Abstract
Cerebral cavernous malformations (CCM) are manifested by microvascular lesions characterized by leaky endothelial
cells with minimal intervening parenchyma predominantly in the central nervous system predisposed to hemorrhagic
stroke, resulting in focal neurological defects. Till date, three proteins are implicated in this condition: CCM1 (KRIT1),
CCM2 (MGC4607), and CCM3 (PDCD10). These multi-domain proteins form a protein complex via CCM2 that function
as a docking site for the CCM signaling complex, which modulates many signaling pathways. Defects in the formation of
this signaling complex have been shown to affect a wide range of cellular processes including cell-cell contact stability,
vascular angiogenesis, oxidative damage protection and multiple biogenic events. In this review we provide an update on
recent advances in structure and function of these CCM proteins, especially focusing on the signaling cascades involved
in CCM pathogenesis and the resultant CCM cellular phenotypes in the past decade.

Keywords: Cerebral cavernous malformation, cerebral cavernous malformation signaling complex, angiogenesis,
endothelial cells, cellular function, microvessel lesions, protein structure, function domain, motif

INTRODUCTION
Cerebral cavernous malformations (CCMs) are vessel dilatations within microvascular beds in the brain that
are predisposed to hemorrhagic stroke. These microvascular malformations are present in 0.5% in the general
population . These lesions are characterized by densely packed tortuous microvessels outlined with deficient
[1]
interstitial brain parenchyma , increasing the propensity of these vascular lesions for leakage . These
[4]
[2,3]
microvascular lesions are predominantly found in the central nervous system (CNS) but are also known to
affect skin and liver. Although it is highly prevalent , a vast majority (approximately 70%) are asymptomatic .
[5]
[1]
© The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0
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