Data from histopathology studies of human atherosclerotic tissue specimens and from vascular imaging studies support the concept that the local arterial microenvironment of a stable atheroma promotes destabilizing conditions that result in the transition to an unstable atheroma. Destabilization is characterized by several different plaque phenotypes that cause major clinical events such as acute coronary syndrome and cerebrovascular strokes. There are several rupture-associated phenotypes causing thrombotic vascular occlusion including simple fibrous cap rupture of an atheroma, fibrous cap rupture at site of previous rupture-and-repair of an atheroma, and nodular calcification with rupture. Endothelial erosion without rupture has more recently been shown to be a common phenotype to promote thrombosis as well. Microenvironment features that are linked to these phenotypes of plaque instability are neovascularization arising from the vasa vasorum network leading to necrotic core expansion, intraplaque hemorrhage, and cap rupture; activation of adventitial and perivascular adipose tissue cells leading to secretion of cytokines, growth factors, adipokines in the outer artery wall that destabilize plaque structure; and vascular smooth muscle cell phenotypic switching through transdifferentiation and stem/progenitor cell activation resulting in the promotion of inflammation, calcification, and secretion of extracellular matrix, altering fibrous cap structure, and necrotic core growth. As the technology evolves, studies using noninvasive vascular imaging will be able to investigate the transition of stable to unstable atheromas in real time. A limitation in the field, however, is that reliable and predictable experimental models of spontaneous plaque rupture and/or erosion are not currently available to study the cell and molecular mechanisms that regulate the conversion of the stable atheroma to an unstable plaque.

来自人类动脉粥样硬化组织标本的组织病理学研究和血管成像研究的数据支持这样的概念：稳定的动脉粥样硬化斑块的局部动脉微环境会促进不稳定的条件，从而导致不稳定的动脉粥样硬化斑块的转变。不稳定的特征是几种不同的斑块表型，这些表型会导致急性冠脉综合征和脑血管中风等重大临床事件。有几种与破裂相关的表型会导致血栓性血管闭塞，包括单纯的动脉粥样硬化纤维帽破裂、动脉粥样硬化先前破裂修复部位的纤维帽破裂以及伴有破裂的结节性钙化。最近显示，不破裂的内皮侵蚀也是促进血栓形成的常见表型。与这些斑块不稳定表型相关的微环境特征是血管滋养管网络产生的新生血管，导致坏死核心扩张、斑块内出血和帽破裂；激活外膜和血管周围脂肪组织细胞，导致外动脉壁分泌细胞因子、生长因子、脂肪因子，从而破坏斑块结构的稳定性；血管平滑肌细胞通过转分化和干细胞/祖细胞激活进行表型转换，从而促进炎症、钙化和细胞外基质的分泌，改变纤维帽结构和坏死核心生长。随着技术的发展，使用无创血管成像的研究将能够实时研究稳定到不稳定动脉粥样硬化的转变。然而，该领域的一个限制是，目前无法使用可靠且可预测的自发斑块破裂和/或侵蚀的实验模型来研究调节稳定粥样斑块转化为不稳定斑块的细胞和分子机制。