Atherosclerosis is the major underlying pathology of cardiovascular disease (CVD). The risk for CVD is increased in women with a history of preeclampsia. Multiple studies have indicated that accelerated atherosclerosis underlies this increased CVD risk. Furthermore, it has been suggested that endothelial dysfunction and inflammation play an important role in the increased CVD risk of women with preeclampsia. Rupture or erosion of atherosclerotic plaques can induce the formation of thrombi that underlie the onset of acute clinical CVD such as myocardial infarction and stroke. In relatively young women, cardiovascular events are mainly due to plaque erosions. Eroded plaques have a distinct morphology compared to ruptured plaques, but have been understudied as a substrate for CVD. The currently available evidence points towards lesions with features of stability such as high collagen content and smooth muscle cells and with distinct mechanisms that further promote the pro-thrombotic environment such as Toll Like Receptor (TLR) signaling and endothelial apoptosis. These suggested mechanisms, that point to endothelial dysfunction and intimal thickening, may also play a role in preeclampsia. Pregnancy is considered a stress test for the cardiovascular system with preeclampsia as an additional pathological substrate for earlier manifestation of vascular disease. This review provides a summary of the possible common mechanisms involved in preeclampsia and accelerated atherosclerosis in young females and highlights plaque erosion as a likely substrate for CVD events in women with a history of preeclampsia.

BackgroundAtherosclerosis is an inflammatory lipid disorder and the main underlying pathology of acute ischemic events. Despite a vast amount of data from murine atherosclerosis models, evidence of B‐cell involvement in human atherosclerotic disease is limited. We therefore investigated the association of circulating B‐cell subtypes with the occurrence of secondary cardiovascular events in advanced atherosclerotic disease.Methods and ResultsThis cohort study consists of 168 patients who were included in the Athero‐Express biobank between 2009 and 2011. Before surgery, peripheral blood mononuclear cells were isolated and stored in liquid nitrogen. After gentle thawing of the peripheral blood mononuclear cells, different B‐cell subtypes including naïve, (un)switched memory, and CD27+ CD43+ B1‐like B cells, were analyzed by flow cytometry. Univariable and multivariable Cox proportional hazard models were used to analyze associations between B‐cell subtypes, circulating antibodies and secondary cardiovascular manifestations during the 3‐year follow‐up period. Mean age was 70.1±9.6 years, males represented 62.8% of the population, and 54 patients had secondary manifestations during follow‐up. High numbers of unswitched memory cells were protective against secondary outcome (hazard ratio, 0.30 [95% CI, 0.13–0.69]; P<0.01). Similar results were obtained for the switched memory cells that also showed to be protective against secondary outcome (hazard ratio, 0.33 [95% CI, 0.14–0.77]; P=0.01).ConclusionsA high number of (un)switched memory B cells is associated with better outcome following carotid artery endarterectomy. These findings suggest a potential role for B‐cell subsets in prediction and prevention of secondary cardiovascular events in patients with atherosclerosis.

NIKEC associate with chronic inflammation in advanced lesions and are linked to markers of local inflammation, lipid content, unstable plaque phenotype and development of MI. Therefore, targeting noncanonical NF-κB signaling may hold therapeutic potential for patients with atherosclerosis and cardiovascular disease.

Mouse studies have established distinct monocyte subtypes that participate in the process of atherosclerotic lesion formation. The pro-inflammatory Ly6C high monocyte subtype actively contributes to murine plaque progression and destabilization. Also in humans, different peripheral monocyte subtypes have been identified, of which the CD14 + CD16 − classical monocyte is suggested to display similar pro-atherosclerotic properties as the murine Ly6C high subtype. We aimed to investigate if circulating CD14 + CD16 − classical monocytes associate with characteristics of a vulnerable carotid atherosclerotic plaque and if they associate with the risk of secondary adverse manifestations of atherosclerotic disease. Methods and results: We enrolled 175 carotid endarterectomy patients of the Athero-Express biobank in our study. Just prior to surgical procedure, blood was collected and peripheral blood mononuclear cells were isolated. Characterization of monocyte subsets was performed by flow cytometry. Plaque characteristics were semiquantitatively scored for the presence of fat, collagen, intraplaque hemorrhage and calcification. Vessel density, smooth muscle cells and macrophages were assessed quantitatively on a continuous scale. All features of a vulnerable plaque phenotype, including low amounts of collagen and smooth muscle cells, and increased fat content, vessel density, intraplaque hemorrhage and plaque macrophages were not significantly associated with differential levels of peripheral classical CD14 + CD16 − monocytes or other monocyte subsets. Using Cox regression models to evaluate the prognostic value of circulating monocyte subtypes, we found that total counts of peripheral monocytes, as well as CD14 + CD16 − classical and other monocyte subtypes were not associated with the risk of secondary cardiovascular events during 3 years follow-up. Conclusion: Circulating classical CD14 + CD16 − monocytes do not associate with specific vulnerable plaque characteristics. In addition, they do not predict secondary adverse manifestations. This suggests that in patients with established carotid artery disease, the circulating monocytes do not reflect plaque characteristics and have no value in identifying patients at risk for future cardiovascular events.