Article

A mechanistic analysis of the role of microcalcifications in atherosclerotic plaque stability: potential implications for plaque rupture.

Department of Biomedical Engineering, The City College of New York, The City University of New York, New York, New York;
AJP Heart and Circulatory Physiology (Impact Factor: 4.01). 07/2012; 303(5):H619-28. DOI: 10.1152/ajpheart.00036.2012
Source: PubMed

ABSTRACT The role of microcalcifications (μCalcs) in the biomechanics of vulnerable plaque rupture is examined. Our laboratory previously proposed (Ref. 44), using a very limited tissue sample, that μCalcs embedded in the fibrous cap proper could significantly increase cap instability. This study has been greatly expanded. Ninety-two human coronary arteries containing 62 fibroatheroma were examined using high-resolution microcomputed tomography at 6.7-μm resolution and undecalcified histology with special emphasis on calcified particles <50 μm in diameter. Our results reveal the presence of thousands of μCalcs, the vast majority in lipid pools where they are not dangerous. However, 81 μCalcs were also observed in the fibrous caps of nine of the fibroatheroma. All 81 of these μCalcs were analyzed using three-dimensional finite-element analysis, and the results were used to develop important new clinical criteria for cap stability. These criteria include variation of the Young's modulus of the μCalc and surrounding tissue, μCalc size, and clustering. We found that local tissue stress could be increased fivefold when μCalcs were closely spaced, and the peak circumferential stress in the thinnest nonruptured cap (66 μm) if no μCalcs were present was only 107 kPa, far less than the proposed minimum rupture threshold of 300 kPa. These results and histology suggest that there are numerous μCalcs < 15 μm in the caps, not visible at 6.7-μm resolution, and that our failure to find any nonruptured caps between 30 and 66 μm is a strong indication that many of these caps contained μCalcs.

0 Bookmarks
 · 
73 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Vascular calcifications (VCs) are actively regulated biological processes associated with crystallization of hydroxyapatite in the extracellular matrix and in cells of the media (VCm) or intima (VCi) of the arterial wall. Both patterns of VC often coincide and occur in patients with type II diabetes, chronic kidney disease, and other less frequent disorders; VCs are also typical in senile degeneration. In this article, we review the current state of knowledge about the pathology, molecular biology, and nosology of VCm, expand on potential mechanisms responsible for poor prognosis, and expose some of the directions for future research in this area.
    European Heart Journal 04/2014; · 14.10 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Circulating microparticles (MPs) have been reported to be associated with coronary artery disease (CAD). In this study, we explored the relationship between MPs procoagulant activity and characteristics of atherosclerotic plaque detected by 64-slice computed tomography angiography (CTA). In 127 consecutive patients with CAD but without acute coronary syndrome and who underwent 64-slice CTA, MPs procoagulant activity in plasma (by a thrombin generation test), soluble form of lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) and N(epsilon)-(carboxymethyl) lysine (CML) circulating levels (by ELISA) were measured. A quantitative volumetric analysis of the lumen and plaque burden of the vessel wall (soft and calcific components), for the three major coronary vessels, was performed. The patients were classified in three groups according to the presence of calcium volume: non-calcified plaque (NCP) group (calcium volume (%) = 0), moderate calcified plaque (MCP) group (0 < calcium volume (%) < 1), and calcified plaque (CP) group (calcium volume (%) ≥ 1). MPs procoagulant activity and CML levels were higher in MCP group than in CP or NCP group (P = 0.009 and P = 0.027, respectively). MPs procoagulant activity was positively associated with CML (r = 0.317, P < 0.0001) and sLOX-1 levels (r = 0.216, P = 0.0025). MPs procoagulant activity was higher in the MCP patient group and correlated positively with sLOX-1 and CML levels, suggesting that it may characterize a state of blood vulnerability that may locally precipitate plaque instability and increase the risk of subsequent major cardiovascular events.
    Journal of Geriatric Cardiology 03/2014; 11(1):13-9.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Most acute coronary syndromes are caused by sudden luminal thrombosis due to atherosclerotic plaque rupture or erosion. Preventing such an event seems to be the only effective strategy to reduce mortality and morbidity of coronary heart disease. Coronary lesions prone to rupture have a distinct morphology compared with stable plaques, and provide a unique opportunity for noninvasive imaging to identify vulnerable plaques before they lead to clinical events. The submillimeter spatial resolution and excellent image quality of modern computed tomography (CT) scanners allow coronary atherosclerotic lesions to be detected, characterized, and quantified. Large plaque volume, low CT attenuation, napkin-ring sign, positive remodelling, and spotty calcification are all associated with a high risk of acute cardiovascular events in patients. Computation fluid dynamics allow the calculation of lesion-specific endothelial shear stress and fractional flow reserve, which add functional information to plaque assessment using CT. The combination of morphologic and functional characteristics of coronary plaques might enable noninvasive detection of vulnerable plaques in the future.
    Nature Reviews Cardiology 04/2014; · 10.40 Impact Factor