Alvaro-González L C, Freijo-Guerrero M M, Sádaba-Garay F
Servicio de Nurología, Hospital de Basurto, Bilbao, España.
Rev Neurol. 2002;35(5):452-62.
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.
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.
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.
动脉粥样硬化是发达国家导致缺血性心脏病和中风，进而造成死亡和残疾的最常见原因。缺血性动脉粥样硬化性血栓形成性中风是其中最常见的形式。从这个意义上讲，我们在此回顾动脉粥样硬化过程的潜在机制。
鉴于罗斯广泛接受的假说，它被理解为一种炎症性疾病：最初从结构角度阐述，因为从疾病的最初阶段（脂纹）到最后复杂阶段，巨噬细胞和T/B淋巴细胞都存在于动脉壁中。起始点是功能性内皮损伤，继发于机械或血管危险因素，称为损伤反应假说。下一步是炎症级联反应，涉及体液（细胞因子、生长因子）和细胞（趋化性增加、炎性细胞黏附和浸润）机制。它们相互作用，失衡且呈渐进性，导致最终的纤维增生性反应。每个阶段都有其自身的炎症成分和相互作用途径。在此过程中以下因素较为突出：1）黏附分子，包括E选择素、细胞间黏附分子1和血管细胞黏附分子1，它们在斑块局部以及作为循环成分增加；IIb/IIIa型血小板受体是属于同一家族的整合素；2）具有促炎活性的细胞因子，如白细胞介素1、肿瘤坏死因子α和淋巴细胞配体如CD40，或具有抗炎活性的细胞因子，如γ干扰素；3）生长因子，以血小板衍生生长因子（PDGF）和成纤维细胞生长因子（FGF）变体为基石；4）全身炎症标志物，总体血浆C反应蛋白和纤维蛋白原，可预测中风和心血管死亡风险；白细胞介素6、补体、凝血酶和热休克蛋白（HSP）的作用类似但不太确切。
炎症在中风中起关键作用的证据使得能够制定预防该疾病的治疗策略：促进天然抗炎机制，或通过选择性（单克隆抗体）或非选择性（IIb/IIIa受体、抗炎药物）途径抑制炎症因子，这些策略有的已初见端倪，有的正在进行，有的已全面发展。
