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[Inflammatory mechanisms, arteriosclerosis and ischemic stroke: clinical data and perspectives]
L C Alvaro-González1, M M Freijo-Guerrero, F Sádaba-Garay
1Servicio de Nurología, Hospital de Basurto, Bilbao, España. lalvaro@hbas.osakidetza.net
Insights
Atherosclerosis, a leading cause of death, is an inflammatory disease. Understanding its inflammatory mechanisms, including key molecules and cellular processes, is crucial for developing effective stroke prevention strategies.
Area of Science:
- Cardiovascular Science
- Immunology
- Pathology
Context:
- Atherosclerosis is a primary cause of mortality and disability in developed nations, frequently leading to ischemic cardiopathy and stroke.
- Ischemic atherothrombotic stroke represents the most prevalent form of stroke.
Purpose:
- This review elucidates the underlying mechanisms of the atherosclerotic process.
- It examines atherosclerosis as an inflammatory disease, supporting the 'response to injury' hypothesis.
Summary:
- The process begins with endothelial dysfunction, followed by an inflammatory cascade involving humoral and cellular factors.
- Key elements include adhesion molecules (E selectin, ICAM 1, VCAM 1), cytokines (IL-1, TNF-a), growth factors (PDGF, FGF), and systemic inflammation markers (C-reactive protein, fibrinogen).
Impact:
- Evidence highlights inflammation's central role in stroke pathogenesis.
- This understanding facilitates the development of targeted therapeutic strategies, including anti-inflammatory approaches and receptor inhibitors, for stroke prevention.
Objective:
The atherosclerosis is the most common cause of death and disability in developed countries by causing ischemic cardiopathic and stroke. The ischemic atherotrombotic stroke is the most frequent form of the last one. In this sense we review herein the mechanisms underlying the artherosclerotic process.
Development:
It is understood as an inflammatory disease, by taking into account the widely accepted hypothesis by Ross: it was firstly stated in structural terms, as macrophages and T/B linfocities were present in the arterial wall from the first stages of the disease (fatty streak) to the last and complicated ones. The starting point is a functional endothelial damage, secondary to mechanical or vascular risk factors and called response to injury hypothesis . The next step is an inflammatory cascade that involves humoral (citokines, growth factors) and cellular (increased quimiotaxis, adherece and infiltration of inflamatory cells) mechanisms. They interact among them, outbalanced and in a progresssive way that leads to the final fibroproliferative response. Every stage has his own inflammatory components and interactive pathways. The following elements are outstanding in this process: 1) Adhesion molecules, including E selectin, ICAM 1 and VCAM 1, that are increased locally in the plaques and as circulating elements; plaquetary receptors of the type IIb/IIIa are integrins wich belong to the same family; 2) Citokines with either proinflammatory activity like IL 1, the TNF a and linfocitary ligands like the CD 40, or with antiinflammatory activity like the gamma interpheron; 3) Growth factors, with plaquetary (PDGF) and fibroblastic (FGF) variants as the cornerstone; 4) Markers of systemic inflammation, overall plasma C reactive protein and fibrinogen, that predict the risk of stroke and cardiovascular death; IL 6, complement, thrombin and heat shock proteins (HSP) would act in a similar but less conclusive way.
Conclusions:
The evidences of the pivotal role of the inflammation in the stroke allow to develop therapeutical strategies to prevent the disease: fostering natural antiinflamatory mechanisms, or inhibiting inflammatory elements by selective (monoclonal antibodies) or non selective (IIb/IIIa receptors, antiinflammatory drugs) pathways are distinctily glimpsed, ongoing or fully developed.