Co-localization of plaque macrophages with calcification is associated with a more vulnerable plaque phenotype and a greater calcification burden in coronary target segments as determined by OCT

Burgmaier, Mathias; Milzi, Andrea; Dettori, Rosalia; Burgmaier, Kathrin; Reith, Sebastian

doi:10.1371/journal.pone.0205984

Cited by 32 publications

(27 citation statements)

References 35 publications

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“…The high levels of inflammatory molecules in CKD might be explained, at least in part, with increased production at tissue level such as at the vascular wall. In atherosclerotic lesions, the accumulation of macrophages within the vascular wall has been consistently co-localized with calcium deposits and associated with various phases of calcification [164,165]. More pronounced macrophage infiltration and higher CRP were described in coronary artery lesions of CKD [166].…”

Section: The Crosstalk Between Vascular Calcification and Inflammatiomentioning

confidence: 99%

The interplay between mineral metabolism, vascular calcification and inflammation in Chronic Kidney Disease (CKD): challenging old concepts with new facts

Viegas

Araújo

Marreiros

et al. 2019

Aging

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Chronic kidney disease (CKD) is one of the most powerful predictors of premature cardiovascular disease (CVD), with heightened susceptibility to vascular intimal and medial calcification associated with a high cardiovascular mortality. Abnormal mineral metabolism of calcium (Ca) and phosphate (P) and underlying (dys)regulated hormonal control in CKD-mineral and bone disorder (MBD) is often accompanied by bone loss and increased vascular calcification (VC). While VC is known to be a multifactorial process and a major risk factor for CVD, the view of primary triggers and molecular mechanisms complexity has been shifting with novel scientific knowledge over the last years. In this review we highlight the importance of calcium-phosphate (CaP) mineral crystals in VC with an integrated view over the complexity of CKD, while discuss past and recent literature aiming to highlight novel horizons on this major health burden. Exacerbated VC in CKD patients might result from several interconnected mechanisms involving abnormal mineral metabolism, dysregulation of endogenous calcification inhibitors and inflammatory pathways, which function in a feedback loop driving disease progression and cardiovascular outcomes. We propose that novel approaches targeting simultaneously VC and inflammation might represent valuable new prognostic tools and targets for therapeutics and management of cardiovascular risk in the CKD population.

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Section: The Crosstalk Between Vascular Calcification and Inflammatiomentioning

confidence: 99%

The interplay between mineral metabolism, vascular calcification and inflammation in Chronic Kidney Disease (CKD): challenging old concepts with new facts

Viegas

Araújo

Marreiros

et al. 2019

Aging

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“…In contrast to macrocalcifications, the presence of spotty microcalcifications detected by IVUS or OCT corresponds with plaque instability. Interestingly, the co-localization of macrophages and microcalcifications in the same plaque was associated with a greater degree of plaque vulnerability, as well as with other features of atherosclerosis, such as increased media thickness, as determined by recent OCT studies [47,48]. Because the same patients showed less advanced coronary artery stenosis, the co-localization of macrophages and microcalcifications is suggestive of an early stage of the atherosclerotic process, which may progress into further calcification and inflammation.…”

Section: Optical Coherence Tomographymentioning

confidence: 78%

Current Advances in the Diagnostic Imaging of Atherosclerosis: Insights into the Pathophysiology of Vulnerable Plaque

Mushenkova¹,

Summerhill

Zhang

et al. 2020

IJMS

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Atherosclerosis is a lipoprotein-driven inflammatory disorder leading to a plaque formation at specific sites of the arterial tree. After decades of slow progression, atherosclerotic plaque rupture and formation of thrombi are the major factors responsible for the development of acute coronary syndromes (ACSs). In this regard, the detection of high-risk (vulnerable) plaques is an ultimate goal in the management of atherosclerosis and cardiovascular diseases (CVDs). Vulnerable plaques have specific morphological features that make their detection possible, hence allowing for identification of high-risk patients and the tailoring of therapy. Plaque ruptures predominantly occur amongst lesions characterized as thin-cap fibroatheromas (TCFA). Plaques without a rupture, such as plaque erosions, are also thrombi-forming lesions on the most frequent pathological intimal thickening or fibroatheromas. Many attempts to comprehensively identify vulnerable plaque constituents with different invasive and non-invasive imaging technologies have been made. In this review, advantages and limitations of invasive and non-invasive imaging modalities currently available for the identification of plaque components and morphologic features associated with plaque vulnerability, as well as their clinical diagnostic and prognostic value, were discussed. Int. J. Mol. Sci. 2020, 21, 2992 2 of 26 by the low and oscillatory endothelial shear stress [3]. According to the current understanding, lesion development involves lipid accumulation in the arterial intima, resulting in foam cell formation, a local inflammatory response, and migration and proliferation of several cell types, including macrophages, smooth muscle cells (SMCs), lymphocytes, neutrophils, and dendritic cells that play a pivotal role in its progression. Lipid accumulation is a key event in the formation of the atherosclerotic lesion, and it is determined by different classes of lipoproteins [4]. Atherosclerotic plaque tends to develop early in life [5], progressing with age; however, the progression rate is not completely predictable and varies among individuals. In general, it undergoes a prolonged asymptomatic phase (lasting many years or several decades) until the manifestation of the first clinical symptoms often at the later stages of atherosclerosis. The mechanisms of plaque progression encompass SMC apoptosis, matrix synthesis, angiogenesis, arterial remodeling, fibrous cap rupture, and thrombosis, followed by necrosis and calcification. The most acute cardiovascular events are triggered by the rupture; erosion; or, the least common, calcified nodule, the vulnerable plaque phenotypes, followed by coronary thrombosis. Ruptured lesions are responsible for the majority (73%) of all ACSs [6]. In addition, the underlying mechanism of sudden coronary death from thrombi was found from plaque erosions, in 30%-35% of cases, and rarely from calcified nodules, in 2%-7% of cases [7].The biological features of two major classes of high-risk (vulnerable) plaques, such as rupture-pron...

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“…Also, OCT is considered the only imaging modality that can directly measure TCFA and quantify the presence of macrophages and cholesterol crystal in the atherosclerotic plaque [20,104,[113][114][115]. OCT imaging of contemporary presence of macrophages and microcalcifications in the same plaque with reciprocal distance smaller than 1 mm (termed co-localization), has been shown to be associated with more vulnerable plaque features [116,117]. These observations seem to indicate that OCT can provide both morphological and disease activity assessment of coronary atherosclerosis.…”

Section: Intravascular Ultrasound (Ivus) and Optical Coherence Tomogrmentioning

confidence: 99%

Coronary Atherosclerosis Imaging

et al. 2020

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Identifying patients at increased risk of coronary artery disease, before the atherosclerotic complications become clinically evident, is the aim of cardiovascular prevention. Imaging techniques provide direct assessment of coronary atherosclerotic burden and pathological characteristics of atherosclerotic lesions which may predict the progression of disease. Atherosclerosis imaging has been traditionally based on the evaluation of coronary luminal narrowing and stenosis. However, the degree of arterial obstruction is a poor predictor of subsequent acute events. More recent techniques focus on the high-resolution visualization of the arterial wall and the coronary plaques. Most acute coronary events are triggered by plaque rupture or erosion. Hence, atherosclerotic plaque imaging has generally focused on the detection of vulnerable plaque prone to rupture. However, atherosclerosis is a dynamic process and the plaque morphology and composition may change over time. Most vulnerable plaques undergo progressive transformation from high-risk to more stable and heavily calcified lesions, while others undergo subclinical rupture and healing. Although extensive plaque calcification is often associated with stable atherosclerosis, the extent of coronary artery calcification strongly correlates with the degree of atherosclerosis and with the rate of future cardiac events. Inflammation has a central role in atherogenesis, from plaque formation to rupture, hence in the development of acute coronary events. Morphologic plaque assessment, both invasive and non-invasive, gives limited information as to the current activity of the atherosclerotic disease. The addition of nuclear imaging, based on radioactive tracers targeted to the inflammatory components of the plaques, provides a highly sensitive assessment of coronary disease activity, thus distinguishing those patients who have stable disease from those with active plaque inflammation.

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Co-localization of plaque macrophages with calcification is associated with a more vulnerable plaque phenotype and a greater calcification burden in coronary target segments as determined by OCT

Cited by 32 publications

References 35 publications

The interplay between mineral metabolism, vascular calcification and inflammation in Chronic Kidney Disease (CKD): challenging old concepts with new facts

The interplay between mineral metabolism, vascular calcification and inflammation in Chronic Kidney Disease (CKD): challenging old concepts with new facts

Current Advances in the Diagnostic Imaging of Atherosclerosis: Insights into the Pathophysiology of Vulnerable Plaque

Coronary Atherosclerosis Imaging

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