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Background: A recent meta-analysis showed that both plasma lipoprotein-associated phospholipase A(2) (Lp-PLA(2) ) mass and activity independently predict cardiovascular events. Notably, Lp-PLA(2) activity but not mass was found to be a determinant of cardiovascular outcome in type 2 diabetes mellitus. We questioned whether relationships of carotid intima media thickness (IMT), a measure of subclinical atherosclerosis, with Lp-PLA(2) mass differ between diabetic and nondiabetic subjects., Materials and Methods: Relationships of IMT with plasma Lp-PLA(2) mass (turbidimetric immunoassay) were compared in 74 patients with type 2 diabetes and in 64 nondiabetic subjects., Results: IMT was increased (P=0·016), but plasma Lp-PLA(2) mass was decreased in patients with diabetes compared to nondiabetic subjects (277±66 vs. 327±62μgL(-1) , P<0·001). In nondiabetic subjects, IMT was correlated positively with Lp-PLA(2) (r=0·325, P<0·009); multiple linear regression analysis confirmed an independent association of IMT with Lp-PLA(2) (ß=0·192, P=0·048). In contrast, IMT was unrelated to Lp-PLA(2) in patients with diabetes (r=0·021, P=0·86), and the relationship of IMT with Lp-PLA(2) was different in diabetic and control subjects (P<0·001). The relationship of Lp-PLA(2) with the total cholesterol/high-density lipoprotein (HDL) cholesterol ratio also differed between diabetic and nondiabetic subjects (P<0·001)., Conclusions: Plasma Lp-PLA(2) may relate to early stages of atherosclerosis development. In diabetes mellitus, in contrast, the association of IMT with plasma Lp-PLA(2) mass is abolished, which could be partly ascribed to redistribution of Lp-PLA(2) mass from apolipoprotein B-containing lipoproteins towards HDL. These findings raise questions about the usefulness of plasma Lp-PLA(2) mass measurement as a marker of subclinical atherosclerosis in type 2 diabetes mellitus., (© 2011 The Authors. European Journal of Clinical Investigation © 2011 Stichting European Society for Clinical Investigation Journal Foundation.)

Many apparent healthy persons die from cardiovascular disease, despite major advances in prevention and treatment of cardiovascular disease. Traditional cardiovascular risk factors are able to predict cardiovascular events in the long run, but fail to assess current disease activity or nearby cardiovascular events. There is a clear relation between the occurrence of cardiovascular events and the presence of so-called vulnerable plaques. These vulnerable plaques are characterized by active inflammation, a thin cap and a large lipid pool. Spectroscopy is an optical imaging technique which depicts the interaction between light and tissues, and thereby shows the biochemical composition of tissues. In recent years, impressive advances have been made in spectroscopy technology and intravascular spectroscopy is able to assess the composition of plaques of interest and thereby to identify and actually quantify plaque vulnerability. This review summarizes the current evidence for spectroscopy as a measure of plaque vulnerability and discusses the potential role of intravascular spectroscopic imaging techniques.

Although cells constantly adapt to external humoral cues, like cytokines and hormones, in practice, most cellular behavior is under locally guided control, via cell-cell interactions. The most prominent members of this group of molecules involved in this intercellular signaling are the galectins, a family of carbohydrate-binding proteins, which by binding specific receptors induce signaling. It has become clear that galectins are important in the pathogenesis of cardiovascular disease, in particular atherosclerosis, stroke, myocardial infarction, and heart failure. Modulation of galectin signaling holds great promise for the treatment of cardiovascular disease as evident from preclinical studies.

Vascular endothelial growth factor (VEGF), a potent growth factor for endothelial cells and inducer of angiogenesis, is important for endothelial integrity and thus for vascular function. On the other hand, VEGF may enhance the pathophysiologic mechanism of plaque formation and plaque destabilization. In this review we discuss the data available so far for VEGF as angiogenic and/or inflammatory cytokine in the vulnerable atherosclerotic plaque.

Background: There is increasing evidence that plaque vulnerability, rather than the degree of stenosis, is important in predicting the occurrence of subsequent cerebral ischemic events in patients with carotid artery stenosis. The many imaging modalities currently available have different properties with regard to the visualization of the extent of vulnerability in carotid plaque formation., Methods: Original published studies were identified using the MEDLINE database (January 1966 to March 2008). Manual cross-referencing was also performed., Results: There is no single imaging modality that can produce definitive information about the state of vulnerability of an atherosclerotic plaque. Each has its own specific drawbacks, which may be the use of ionizing radiation or nephrotoxic contrast agents, an invasive character, low patient tolerability, or simply the paucity of information obtained on plaque vulnerability. Functional molecular imaging techniques such as positron emission tomography (PET), single photon emission-computed tomography (SPECT) and near infra-red spectroscopy (NIRS) do seem able accurately to visualize and even quantify features of plaque vulnerability and its pathophysiologic processes. Promising new techniques like near infra-red fluorescence imaging are being developed and may be beneficial in this field., Conclusion: There is a promising role for functional molecular imaging modalities like PET, SPECT, or NIRS related to improvement of selection criteria for carotid intervention, especially when combined with CT or MRI to add further anatomical details to molecular information. Further information will be needed to define whether and where this functional molecular imaging will fit into a clinical strategy.

Purpose: In this study, the potential of matrix metalloproteinase (MMP) sense for detection of atherosclerotic plaque instability was explored. Secondly, expression of MMPs by macrophage subtypes and smooth muscle cells (SMCs) was investigated.Procedures: Twenty-three consecutive plaques removed during carotid endarterectomy were incubated in MMPSense™ 680 and imaged with IVIS® Spectrum. mRNA levels of MMPs, macrophage markers, and SMCs were determined in plaque specimens, and in in vitro differentiated M1 and M2 macrophages.Results: There was a significant difference between autofluorescence signals and MMPSense signals, both on the intraluminal and extraluminal sides of plaques. MMP-9 and CD68 messenger RNA (mRNA) expression was higher in hot spots, whereas MMP-2 and αSMA expression was higher in cold spots. In vitro M2 macrophages had higher mRNA expression of MMP-1, MMP-9, MMP-12, and TIMP-1 compared to M1 macrophages.Conclusion: MMP-9 is most dominantly MMP present in atherosclerotic plaques and is produced by M2 rather than M1 macrophages. [ABSTRACT FROM AUTHOR]

TLR (Toll-like receptor) activation-induced inflammatory responses are important in the progression of atherosclerosis. We previously showed that TLR-dependent leucocyte responsiveness is acutely attenuated following percutaneous coronary intervention or vascular surgery. Furthermore, cytokine release following whole-blood TLR-2 and TLR-4 stimulation is negatively correlated with fractional flow reserve, suggesting that chronic ischaemia can elicit an enhanced inflammatory response. In the present study, we assessed the association between leucocyte TLR-2 and TLR-4 responsiveness and pre-existent and inducible ischaemia in patients undergoing SPECT (single-photon emission computed tomography)-MPI (myocardial perfusion imaging). TLR-2, TLR-4 and CD11b expression on monocytes were measured in blood samples that were obtained from 100 patients with suspected coronary artery disease before and after myocardial stress testing for SPECT-MPI. IL-8 (interleukin-8) levels were determined after whole-blood stimulation with Pam3Cys (TLR-2) and LPS (lipopolysaccharide; TLR-4). On the basis of SPECT-MPI, patients were categorized into three groups: reversible defect, irreversible defect and no defect. Myocardial stress induced a reduction in TLR-4 expression (2.46±0.21 compared with 2.17±0.16 arbitrary units, P=0.001) and CD11b expression (83.2±1.73 compared with 76.0±1.89 arbitrary units, P<0.001). TLR-induced IL-8 production before myocardial stress induction was not associated with the results of SPECT-MPI. However, a significant decrease in IL-8 production following TLR stimulation was observed after stress, which was more pronounced in patients with a reversible defect. In conclusion, inducible ischaemia is associated with a decrease in whole-blood TLR-2 and TLR-4 response. These results point to a regulating role of TLRs in order to prevent excessive inflammatory events known to occur during acute ischaemia. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are tiny, endogenous nucleotides that bind to mRNA and induce translation repression within metazoan cells. Since their discovery in 1993 in Caenorhabditis elegans and the demonstration of miRNAs in Homo sapiens in 2000, research has been fruitful in deciphering the role of these nucleotides in development, tissue homeostasis, and pathologic processes. In humans, around 700 human miRNA nucleotides have been verified, which interfere with 30% of all genes. Recently, the role of miRNA in cardiovascular research gained attention and the involvement of miRNAs in several cardiovascular diseases has been identified. In this review, we focus on the role of miRNAs in atherosclerosis and in particular on the potential role of miRNAs in the development of vulnerable atherosclerotic plaques. The role of miRNA in the main characteristics of these plaques, inflammation, angiogenesis, and apoptosis will be discussed. Finally, the future perspectives and miRNA-based diagnostic and therapeutic potentials will be highlighted. [Copyright &y& Elsevier]

Patients with chronic renal failure have increased cardiac calcium loads. Previous studies have investigated the prevalence and quantitative extent of aortic valve calcium (AVC) and coronary artery calcium (CAC) in patients with various stages of chronic kidney disease (CKD). However, the impact of preexisting atherosclerosis on the calcification burden has not been clarified. Therefore, this study was conducted to examine the effect of CKD stage as well as the primary cause of renal failure (atherosclerotic vs nonatherosclerotic) on AVC and CAC. Twenty-two, 13, and 28 patients with stage 3, 4, and 5 CKD, respectively, were included, of whom 24 had atherosclerotic CKD. Patients underwent electron-beam computed tomography to assess AVC and CAC. AVC was present in 27% of patients with stage 3 CKD, in 38% of patients with stage 4 CKD, and in 43% of patients with stage 5 CKD. CAC was present in 77% of patients with stage 3 CKD, in 54% of patients with stage 4 CKD, and in 64% of patients with stage 5 CKD. There was no correlation between CKD stage and the quantitative extent of AVC and CAC. AVC was more frequent (58% vs 23%, p <0.01) and more extensive (median score 43 [range 0 to 494] vs 0 [range 0 to 8], p <0.01) in patients with CKD caused by atherosclerotic renal disease than in patients with nonatherosclerotic causes of CKD. CAC was more frequent (83% vs 56%, p <0.05) and more extensive (median score 437 [range 61 to 1,565] vs 31 [range 0 to 155], p <0.001) in patients with atherosclerotic causes of CKD than in patients with CKD caused by nonatherosclerotic renal disease. In conclusion, the prevalence as well as the severity of AVC and CAC did not vary between patients with stage 3, 4, and 5 CKD. Cardiac calcification, both AVC and CAC, were more frequent and more severe in patients with atherosclerotic causes of renal failure. These results suggest that cardiac calcium is related to atherosclerotic burden rather than to the severity of CKD. [Copyright &y& Elsevier]