Biomechanics and Inflammation in Atherosclerotic Plaque Erosion and Plaque Rupture: Implications for Cardiovascular Events in Women

Abstract

ObjectiveAlthough plaque erosion causes approximately 40% of all coronary thrombi and disproportionally affects women more than men, its mechanism is not well understood. The role of tissue mechanics in plaque rupture and regulation of mechanosensitive inflammatory proteins is well established, but their role in plaque erosion is unknown. Given obvious differences in morphology between plaque erosion and rupture, we hypothesized that inflammation in general as well as the association between local mechanical strain and inflammation known to exist in plaque rupture may not occur in plaque erosion. Therefore, our objective was to determine if similar mechanisms underlie plaque rupture and plaque erosion.Methods and ResultsWe studied a total of 74 human coronary plaque specimens obtained at autopsy. Using lesion-specific computer modeling of solid mechanics, we calculated the stress and strain distribution for each plaque and determined if there were any relationships with markers of inflammation. Consistent with previous studies, inflammatory markers were positively associated with increasing strain in specimens with rupture and thin-cap fibroatheromas. Conversely, overall staining for inflammatory markers and apoptosis were significantly lower in erosion, and there was no relationship with mechanical strain. Samples with plaque erosion most closely resembled those with the stable phenotype of thick-cap fibroatheromas.ConclusionsIn contrast to classic plaque rupture, plaque erosion was not associated with markers of inflammation and mechanical strain. These data suggest that plaque erosion is a distinct pathophysiological process with a different etiology and therefore raises the possibility that a different therapeutic approach may be required to prevent plaque erosion.

High wall shear stress and high-risk plaque: an emerging concept

“…Eruptive calcified nodules are the less common cause of thrombosis [5]. While recent analyses suggest different etiologies for plaque rupture and plaque erosion [5,9,10], mechanisms of plaque rupture have been extensively studied and morphological features of rupture-prone plaques are well established (Table 1) [8]. No single morphological features have been identified for erosion-prone plaques; nevertheless, we know that eroded plaques with thrombosis are rarely calcified or associated with expansive remodeling, and show minimal inflammation [8,11].…”

“…In line with the experimental and autopsy studies, longitudinal and cross-sectional human coronary and carotid studies have shown an increase in plaque necrotic core, calcium [35], and strain [45], development of expansive remodeling [35,46], presence of IPH [47], large necrotic core [34,46,48], a necrotic core in contact with the lumen [48], and napkin-ring sign [46] in areas exposed to high WSS. Meanwhile, some data show that WSS might not have the same role in development of plaque erosion as it has in the development of plaque rupture [9,10]. …”

Inflammatory Differences in Plaque Erosion and Rupture in Patients With ST‐Segment Elevation Myocardial Infarction

“…Autopsy studies suggest that markers of inflammation are significantly lower in plaque erosion compared with plaque rupture, with sparse infiltration of macrophages and T lymphocytes within the vessel wall . Other studies, however, have suggested an important role for neutrophil infiltrates at sites of plaque erosion .…”

Myocardial Infarction in Young Patients: Causes and Prognosis

“…В результате проведения морфологических исследований активированные макрофаги, тучные клетки и тканевой фактор в большом количестве обнаруживаются именно в области разрыва. Эрозия бляшки не связана так тесно, как разрыв, с активностью системного и местного воспаления и апоптоза [17]. Механизмы возникновения эрозии на поверхности бляшки менее изучены, но определенно в этом процессе имеют значение разрушение и перестройка внеклеточного матрикса.…”