Toshio Imanishi

Peripheral artery disease (PAD) is an inflammatory disease caused by atherosclerosis. It has been demonstrated that PAD is related to chronic inflammation. While conventional risk factors lead to the pathogenesis and progression of PAD, the role of novel inflammatory biomarkers in relation to PAD is being increasingly recognized. The novel biomarkers for PAD may allow for earlier screening and detection, suppression of disease progression, and development of new therapeutic approaches. In this review, inflammatory biomarkers that should be contributory to diagnosis, prognosis, and avenues for therapeutic challenges in PAD are summarized.

Background: It remains unclear whether glycemic fluctuation immediately after acute myocardial infarction (AMI) can affect myocardial damage. This study investigated the impact of glucose fluctuation on myocardial salvage following successful recanalization of primary AMI. Methods and Results: A total of 36 consecutive patients with AMI were studied. Glycemic variability, as indicated by the mean amplitude of glycemic excursion (MAGE), was measured on a continuous glucose monitoring system. Three subsets (CD14+CD16−, CD14++CD16+ and CD14+−CD16+) were measured on flow cytometry 1, 2, 3, 4 and 5 days after AMI onset. A 2-h oral glucose test was performed in 23 patients who had no previous diagnosis of diabetes and/or glycated hemoglobin <6.5%, after the onset of AMI at 2 weeks. Plasma active glucagon-like peptide (GLP)-1 level was measured in each sample. The extent of myocardial salvage 7 days after AMI was evaluated on cardiovascular magnetic resonance imaging. MAGE and the peak CD14+CD16− monocyte level were significantly negatively correlated with myocardial salvage index (MSI). MAGE was significantly correlated with peak CD14+CD16− monocyte level. Of interest, plasma GLP-1 level was significantly positively correlated with MSI and significantly negatively correlated with MAGE. Conclusions: Glucose fluctuations during the acute phase of AMI affect MSI, indicating that manipulation of glucose variability from peak to nadir might be a potential therapeutic target for salvaging ischemic damage. (Circ J 2014; 78: 170–179)

Abstract: Peripheral arterial disease (PAD) is due to diffuse atherosclerosis. The pathological process is characterized mainly by the aberrant proliferation of vascular smooth muscle cells and the formation of neointimal lesions. MicroRNAs (miRNAs) are highly conserved non-coding small RNA molecules that regulate a large fraction of the genome by binding to complementary mRNA sequences, resulting in post-transcriptional gene silencing. Recent evidence has demonstrated that specific miRNAs are involved in the pathological development of PAD. In this review, the roles of specific miRNAs in PAD are summarized.

Atherosclerosis is characterized by chronic inflammation of the vascular wall. Macrophages, which differentiate from circulating monocytes, give rise to foam cells by excessive accumulation of modified lipoproteins. Atherogenesis subsequently progresses through necrotic core expansion associated with apoptosis and the suppressed clearance of apoptotic macrophage (i.e. efferocytosis), followed by the transition to vulnerable plaques. The vulnerable plaque is characterized by thinning of the fibrous cap and necrotic core expansion. Here, the impact of monocytes/macrophages in both early atherogenesis and advanced plaque progression is discussed with a focus on the potential targeting of inflammatory processes in atherosclerosis.

Atherogenesis progresses through lipid core expansion and macrophage accumulation at the plaque, leading to fibrous cap rupture. Plaque rupture occurs in the plaque fissuring at one point, which ultimately brings the platelets into contact with the content of the lipid core, and the blood coagulation factors together with tissue factor. The transition from stable atherosclerotic plaques to vulnerable plaques finally resulting in the plaque rupture is the consequence of an inflammatory reaction. This process involves complex cellular interactions engaging many mediators, chemokines, and cytokines which can be measured in serum and plasma and thus serve as biomarkers that differentiate the pathophysiologic phases of disease progression. Pathological studies support the risk of inflammation in high-risk patients to a greater extent than the degree of vessel stenosis. It is therefore important to identify reliable biomarkers allowing us to monitor vascular inflammatory state. In clinical investigations, several new biomarkers have been identified that provide increasing diagnostic and prognostic significance. However, more confirmatory studies are required to clinical use. Furthermore, assays for automated use need to be developed, and cut-off levels need to be defined. Further technological advances will likely facilitate the use of multimarker profiling to identify with coronary vulnerable plaque.

Background: It remains unclear whether angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II type 1 receptor blockers (ARBs) have fully delivered the expected reduction in cardiovascular diseases. We investigated the effects of adding the direct renin inhibitor (DRI), aliskiren, to an ACEI or an ARB on monocyte subsets and myocardial salvage in patients with primary acute myocardial infarction (AMI). Methods and Results: Twenty-one consecutive patients were treated with an ACEI or an ARB (non-DRI group), and another 21 consecutive patients received aliskiren combined with an ACEI or an ARB (DRI group). Two monocyte subsets (CD14+CD16- and CD14+CD16+) were measured by flow cytometry. The extent of myocardial salvage 7 days after AMI was evaluated by cardiac magnetic resonance imaging. Both plasma renin activity and aldosterone levels were significantly lower in the DRI group than in the non-DRI group. Peak levels of CD14+CD16- monocyte number and ratio were also significantly lower in the DRI group. The extent of myocardial salvage was significantly higher in the DRI group than in the non-DRI group (44.8 [41.2-53.1] vs. 36.0 [28.5-42.6], P=0.001). Conclusions: A DRI combined with an ACEI or an ARB can better improve the extent of myocardial salvage after AMI than an ACEI or an ARB alone in association with the decrease in circulating CD14+CD16- monocytes. (Circ J 2012; 76: 1461-1468)