Relation of arterial geometry to luminal narrowing and histologic markers for plaque vulnerability: the remodeling paradox

AbstractObjective. To relate local arterial geometry with markers that are thought to be related to plaque rupture.Background. Plaque rupture often occurs at sites with minor luminal stenosis and has retrospectively been characterized by colocalization of inflammatory cells. Recent studies have demonstrated that luminal narrowing is related with the mode of atherosclerotic arterial remodeling.Methods. We obtained 1,521 cross section slices at regular intervals from 50 atherosclerotic femoral arteries. Per artery, the slices with the largest and smallest lumen area, vessel area and plaque area were selected for staining on the presence of macrophages (CD68), T-lymphocytes (CD45RO), smooth muscle cells (alpha-actin) and collagen.Results. Inflammation of the cap or shoulder of the plaque was observed in 33% of all cross sections. Significantly more CD68 and CD45RO positive cells, more atheroma, less collagen and less alpha-actin positive staining was observed in cross sections with the largest plaque area and largest vessel area vs. cross sections with the smallest plaque area and smallest vessel area, respectively. No difference in the number of inflammatory cells was observed between cross sections with the largest and smallest lumen area.Conclusion. Intraindividually, pathohistologic markers previously reported to be related to plaque vulnerability were associated with a larger plaque area and vessel area. In addition, inflammation of the cap and shoulder of the plaque was a common finding in the atherosclerotic femoral artery

Discrimination of intravascular lumen and dissections in single intravascular ultrasound images using subtraction, conventional averaging and saline flush

With current 30-MHz intravascular ultrasound systems, flowing blood may cause considerable backscatter which in real-time images is characterized by dynamic speckle. However, in a single intravascular ultrasound image (still-frame) the discrimination between arterial lumen and wall may be difficult due to the frozen intraluminal speckle, particularly in the presence of dissections. We compared subtraction, averaging and saline flush as methods to improve the discrimination between arterial lumen and wall in a single image. The real-time images served as gold standard. In 22 patients who underwent peripheral balloon angioplasty, ultrasound images obtained from 84 sites were examined. The sensitivity and specificity of detecting dissections were in the subtraction image 85% and 100%, in the averaged image 57% and 96%, and in the saline flush image 58% and 86%, respectively. Subtraction is a promising method to outline the irregular lumen in a single image

Shear-stress and wall-stress regulation of vascular remodeling after balloon angioplasty: effect of matrix metalloproteinase inhibition

BACKGROUND: Constrictive vascular remodeling (VR) is the most significant component of restenosis after balloon angioplasty (PTA). Whereas in physiologi

Inflammation of the atherosclerotic cap and shoulder of the plaque is a common and locally observed feature in unruptured plaques of femoral and coronary arteries

Retrospectively, plaque rupture is often colocalized with inflammation of the cap and shoulder of the atherosclerotic plaque. Local inflammation is therefore considered a potential marker for plaque vulnerability. However, high specificity of inflammation for plaque rupture is a requisite for application of inflammation markers to detect rupture-prone lesions. The objective of the present study was to investigate the prevalence and distribution (local versus general) of inflammatory cells in nonruptured atherosclerotic plaques. The cap and shoulder of the plaque were stained for the presence of macrophages and T lymphocytes in 282 and 262 cross sections obtained from 74 coronary and 50 femoral arteries, respectively. From most cases, 2 atherosclerotic arteries were studied to gain insight into the local and systemic distribution of the inflammatory process. In 45% and 41% of all cross sections, staining for macrophages was observed in the femoral and coronary arteries, respectively. Rupture of the fibrous cap was observed in 2 femoral and 3 coronary artery segments and was always colocalized with inflammatory cells. At least 1 cross section stained positively for CD68 or acid phosphatase in 84% and 71% of all femoral and coronary arteries, respectively. Only 1 femoral and 6 coronary arteries revealed a positive stain for CD68 in all investigated segments. Inflammation of the cap and shoulder of the plaque is a common feature, locally observed, in atherosclerotic femoral and coronary arteries. The high prevalence of local inflammatory responses should be considered if they are used as a diagnostic target to detect vulnerable, rupture-prone lesions

Associations of autozygosity with a broad range of human phenotypes

Abstract: In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding