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Lipoprotein(a) is an apolipoprotein B100-containing low-density lipoprotein-like particle that is rich in cholesterol, and is associated with a second major protein, apolipoprotein(a). Apolipoprotein(a) possesses structural similarity to plasminogen but lacks fibrinolytic activity. As a consequence of its composite structure, lipoprotein(a) may: (1) elicit a prothrombotic/antifibrinolytic action favouring clot stability; and (2) enhance atherosclerosis progression via its propensity for retention in the arterial intima, with deposition of its cholesterol load at sites of plaque formation. Equally, lipoprotein(a) may induce inflammation and calcification in the aortic leaflet valve interstitium, leading to calcific aortic valve stenosis. Experimental, epidemiological and genetic evidence support the contention that elevated concentrations of lipoprotein(a) are causally related to atherothrombotic risk and equally to calcific aortic valve stenosis. The plasma concentration of lipoprotein(a) is principally determined by genetic factors, is not influenced by dietary habits, remains essentially constant over the lifetime of a given individual and is the most powerful variable for prediction of lipoprotein(a)-associated cardiovascular risk. However, major interindividual variations (up to 1000-fold) are characteristic of lipoprotein(a) concentrations. In this context, lipoprotein(a) assays, although currently insufficiently standardized, are of considerable interest, not only in stratifying cardiovascular risk, but equally in the clinical follow-up of patients treated with novel lipid-lowering therapies targeted at lipoprotein(a) (e.g. antiapolipoprotein(a) antisense oligonucleotides and small interfering ribonucleic acids) that markedly reduce circulating lipoprotein(a) concentrations. We recommend that lipoprotein(a) be measured once in subjects at high cardiovascular risk with premature coronary heart disease, in familial hypercholesterolaemia, in those with a family history of coronary heart disease and in those with recurrent coronary heart disease despite lipid-lowering treatment. Because of its clinical relevance, the cost of lipoprotein(a) testing should be covered by social security and health authorities.

Cryptogenic stroke is an old definition that designates an ischemic stroke with no identifiable cause. The term of the embolic stroke of undetermined source was then introduced to identify non-lacunar strokes in whom thromboembolism was the likely mechanism. This subgroup of cryptogenic strokes remains heterogeneous with many potential and possibly associated embolic causes. Covert atrial fibrillation is probably less often involved than initially expected, in contrast to intracranial and extracranial atherosclerosis. The cardiologist should be involved in the search of underlying causes of ischemic stroke by helping the neurologist to identify the most likely diagnosis. Further research is necessary to select populations that may benefit from more effective and individualized treatment.

NLRP3 and PPARγ play important roles in the development of atherosclerosis (AS). Studies have shown that PPARγ regulates the expression of NLRP3 in vascular diseases. In addition, the adipocyte factor CTRP6 can improve the activation of PPARγ in vascular diseases. However, the regulatory relationship between CTRP6, PPARγ, and NLRP3 in AS and its underlying mechanism have not been reported. Since proliferation, migration, and dedifferentiation of vascular smooth muscle cells (VSMCs) are key events in AS, in this study, we induced proliferation, migration, and dedifferentiation of VSCMs through homocysteine (HCY) to detect the specific effects of CTRP6, PPARγ, and NLRP3. Subsequently, CTRP6 was overexpressed and the PPARγ inhibitor GW9662 and agonist rosiglitazone were administered to HCY-induced VSCMs to investigate the mechanisms. The results show that the expression of CTRP6 decreased in HCY-induced VSMCs. In addition, CTRP6 overexpression inhibited the proliferation and migration of HCY-induced VSMCs, as well as cell cycle acceleration and dedifferentiation. Overexpression of CTRP6 increased HCY-induced PPARγ expression and inhibited NLRP3 expression. The addition of GW9662 and rosiglitazone further demonstrated that overexpression of CTRP6 inhibited HCY-induced VSMC proliferation, migration, and dedifferentiation through PPARγ/NLRP3 signaling. In conclusion, CTRP6 inhibited HCY-induced proliferation, migration, and dedifferentiation of VSMCs through PPARγ/NLRP3.

BACKGROUND: QRS fragmentation (fQRS) represents a marker of local myocardial fibrosis, especially in patients with CAD (coronary artery disease). However, little is known about the association between fQRS and the severity of coronary atherosclerosis as defined by the Gensini score.
OBJECTIVE: To identify the angiographic and echocardiographic characteristics of patients with suspected CAD depending on the location and extent of fQRS.
METHODS: A total of 178 patients who underwent coronary angiography were included in the study. fQRS was defined as the presence of RSR\' and/or notching of the R/S wave (if QRS<120ms) or≥2 notches of the R/S wave (if QRS≥120ms). All patients were divided into three groups: non-fQRS; fQRS in 1-2 and≥3 leads.
RESULTS: Statistically significant differences in the LVEF (left ventricular ejection fraction, P=0.009) and the degree of coronary atherosclerosis severity (P=0.008) were found among 3 groups. The median Gensini score was 7 in non-fQRS group (minimal CAD) and >20 in other groups (severe CAD). Both the anterior and lateral fQRS groups had a lower LVEF compared to no fQRS (P=0.039 and P=0.01, respectively). The median Gensini score was significantly higher in case of the lateral fQRS (P=0.037). fQRS in≥1 lead was associated with coronary occlusion (OR 2.1, 95% CI: 1.1-4.1, P=0.038).
CONCLUSIONS: The presence of fQRS, particularly in lateral leads, can be a useful noninvasive marker of severe coronary atherosclerosis. Patients with≥1 fragmented lead have a lower LVEF, a higher Gensini score and a two-fold increased risk of occlusion.

Cardiovascular diseases, particularly atherothrombosis, are the leading cause of death worldwide, but their mechanisms are not yet fully understood. Traditional cardiovascular risk factors have been known for many years, but are not enough to predict individual risk. Clonal haematopoiesis of indeterminate potential (CHIP) has been described recently; it corresponds to the clonal expansion of a population of haematopoietic cells in response to the acquisition of a somatic mutation, without any clinical or biological sign of haematological malignancy. The prevalence of this condition increases with age, reaching 10-20% of the general population aged>70 years. Recent observational studies have shown a link between CHIP and cardiovascular diseases in humans, revealing that CHIP carriers have a higher risk of myocardial infarction, heart failure and severe aortic valve stenosis. The prognosis of these conditions also seems to be altered by the presence of CHIP. Experimental studies have identified that the immune system and inflammation - particularly interleukin-1β-secreting macrophages - play a critical role in enhancing the cardiovascular consequences of CHIP, through their action on the atherosclerotic plaque and myocardial tissues. We aimed to write an extensive review of what is currently known about CHIP and its cardiovascular consequences, the pathophysiological mechanisms leading to the increased cardiovascular risk and, finally, the expected influence on our daily practice and how we care for patients with CHIP.

There are controversies in the literature on the blood supply to the forearm after surgical removal of the radial artery in coronary artery bypass grafting (CABG). The objective was to investigate the arterial remodeling of the ulnar artery after the removal of the radial artery in myocardial revascularization by means of ultrasound examination with color Doppler in the pre- and post-operative periods. This paper describes an observational prospective study of the remodeling of the left brachial and ulnar arteries (donor arm) in 103 right-handed non-consecutive adult patients undergoing CABG with removal of the ipsilateral radial artery using the color Doppler ultrasound examination. In the ulnar artery, a significant increase (P < 0.05) was seen in the following measurements: lumen diameter by 13%, lumen area by 26%, peak systolic flow by 40%, and average flow by 46%. Intima-media thickness measured in the ulnar artery did not show a statistically significant difference (P = 0.22), except in diabetic patients (P = 0.007). We conclude that the ulnar artery undergoes positive physiological remodeling, adapting to the new requirements of chronic increase in flow after the ipsilateral removal of the radial artery to serve as a graft in CABG. There was no evidence of increased intima-media thickness, except in diabetic patients.

Atherosclerosis (AS) is a chronic inflammatory disease that involves cell death and endothelial dysfunction. Melatonin is an endocrine hormone with anti-inflammatory and anti-AS effects. However, the underlying molecular mechanisms for the anti-AS effects of melatonin are unknown. A previous study has shown that pyroptosis plays a detrimental role in the development of AS, therefore, this study was designed to investigate the anti-pyroptotic effects and potential mechanisms of melatonin in atherosclerotic endothelium. Our results show that melatonin attenuated the expression of genes related to pyroptosis, including NLRP3, caspase-1, and IL-1β, in human umbilical vein endothelial cells treated with oxidized low-density lipoprotein. Furthermore, melatonin up-regulated the expression of ten-eleven translocation 2 (TET2), inhibited the methylation of ubiquinol-cytochrome c reductase core protein 1 (UQCRC1), and reduced pyroptosis. The up-regulation of UQCRC1 by melatonin improved mitochondrial function, thereby inhibiting oxidative stress and endothelial cell pyroptosis. Collectively, our results indicate that melatonin prevents endothelial cell pyroptosis by up-regulating TET2 to inhibit the methylation of UQCRC1 and improving mitochondrial function.

Cardiac CT-scan is recommended for sorting patients presenting with stable or acute chest pain with low to intermediate risk of coronary artery disease (CAD). Recent studies have shown its reliability for diagnosing CAD in high-risk patients, notably those with acute coronary syndrome (ACS) without ST-elevation. Coronary CT-scan also represents a great opportunity for the screening of atherosclerosis in patients at risk and allows a better prevention of coronary artery disease by introduction of preventive treatments in patients with abnormal coronary CT-scan, especially statins. It is useful for the follow-up of patients who underwent a coronary arteries revascularization with either stents or bypasses. Coronary arteries calcium scoring appears to be an independent predictive factor of cardiovascular and total mortality and its use is recommended for stratifying the cardiovascular risk. However, its interpretation remains unobvious and the patient management is poorly improved by the results. Anyway, if the score is above zero, atherosclerosis is present and therefore a lipid lowering treatment should be discussed. Cardiac CT-scan has become the Gold Standard exam before an aortic valve replacement, for the measurement of the aortic root notably, allowing the best prothesis selection. Before atrial fibrillation ablation procedure by pulmonary vein isolation, the cardiac CT-scan allows a 3-D visualization of the two atria, especially the left atrium, and rules out any suspicion of cardiac thrombus. It allows the research of an anomalous pulmonary venous connection. The 3-D support will also enable the operator to navigate in the heart during the ablation procedure.

Human arterial endothelial cells (HAECs) regulate their phenotype by integrating signals encoded in the frictional forces exerted by flowing blood, fluid shear stress (FSS). High laminar FSS promotes establishment of adaptive HAEC phenotype protective against atherosclerosis, whereas low or disturbed FSS cause HAECs to adopt atheroprone phenotypes. A vascular endothelial cadherin (VE cadherin)-based mechanosensory complex allows HAECs to regulate barrier function, cell morphology,/ and gene expression in response to FSS. Previously, we reported that this mechanosensor integrated exchange protein activated by cAMP (EPAC1) and a PDE4D gene derived cyclic nucleotide phosphodiesterase (PDE), but had not identified the PDE4D variant involved. Our hypothesis here was that only one of the two ∼100 kDa PDE4D variants expressed in HAECs coordinated these responses. Now, we show one unique PDE4D splice variant, PDE4D7, controls transcriptional responses of HAECs to FSS while another, PDE4D5, does not. Adaptive transcriptional responses of HAECs subjected to laminar FSS in vitro were blunted in cells in which PDE4D7 was silenced, but unaffected in cells with silenced PDE4D5. This work identifies a specific therapeutic target for the treatment or prevention of atherosclerosis and improves our understanding of the role of cAMP signaling in modulating mechanosensory signal transduction in the vascular endothelium.