Biology of intracranial aneurysms: role of inflammation.
Intracranial aneurysms (IAs) linger as a potentially devastating clinical problem. Despite intense investigation, our understanding of the mechanisms leading to aneurysm development, progression and rupture remain incompletely defined. An accumulating body of evidence implicates inflammation as a critical contributor to aneurysm pathogenesis. Intracranial aneurysm formation and progression appear to result from endothelial dysfunction, a mounting inflammatory response, and vascular smooth muscle cell phenotypic modulation producing a pro-inflammatory phenotype. A later final common pathway appears to involve apoptosis of cellular constituents of the vessel wall. These changes result in degradation of the integrity of the vascular wall leading to aneurysmal dilation, progression and eventual rupture in certain aneurysms. Various aspects of the inflammatory response have been investigated as contributors to IA pathogenesis including leukocytes, complement, immunoglobulins, cytokines, and other humoral mediators. Furthermore, gene expression profiling of IA compared with control arteries has prominently featured differential expression of genes involved with immune response/inflammation. Preliminary data suggest that therapies targeting the inflammatory response may have efficacy in the future treatment of IA. Further investigation, however, is necessary to elucidate the precise role of inflammation in IA pathogenesis, which can be exploited to improve the prognosis of patients harboring IA.
Joseph and Marie Field Cerebrovascular Research Laboratory, Division of Neurovascular and Endovascular Surgery, Department of Neurological Surgery, Thomas Jefferson University and Jefferson Hospital for Neuroscience, Philadelphia, Pennsylvania 19107, USA. aaron.dumont@jefferson.edu
Nohra
N
Chalouhi
Muhammad S
MS
Ali
Pascal M
PM
Jabbour
Stavropoula I
SI
Tjoumakaris
L Fernando
LF
Gonzalez
Robert H
RH
Rosenwasser
Walter J
WJ
Koch
Aaron S
AS
Dumont
D000818:Animals; D001921:Brain / Q000473:pathology; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D018836:Inflammation Mediators / Q000502:physiology; D002532:Intracranial Aneurysm / Q000188:drug therapy / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D009131:Muscle, Smooth, Vascular / Q000473:pathology / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D018836:Inflammation Mediators