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PubMed2004

Chemokines: key regulators of mononuclear cell recruitment in atherosclerotic vascular disease.

Understanding the increasingly complex role of chemokines in various manifestations of atherosclerotic vascular disease and the apparent redundancy in their expression requires improved concepts defining the specialization and cooperation of chemokines in regulating the recruitment of mononuclear cells to vascular lesions. In an attempt to elaborate such models, this review highlights recent insights into the functional role of chemokines in mediating distinct steps during the atherogenic recruitment of monocytes and T cells obtained in genetically deficient mice and in suitable models. A particular focus is placed on the contribution of platelet chemokines deposited on endothelium for monocyte arrest, on differences in the involvement of chemokines between recruitment to native lesions and to neointimal lesions after arterial injury, and on closely related functions of macrophage migration inhibitory factor, a cytokine with considerable structural homology to chemokines. As an evolving aspect of atherosclerotic vascular disease, a role of chemokines, foremost stromal cell-derived factor-1alpha, in the recruitment of mononuclear progenitors of vascular cells during neointimal hyperplasia, endothelial recovery, and angiogenesis is discussed. The functional diversity and pleiotropy of chemokines in and beyond mononuclear cell recruitment awaits further elucidation to enable therapeutic targeting of atherogenesis by context-specific blockade of nonoverlapping chemokine receptor pairs.

Animals↗

PubMed2001

The fetal cardiac isovolumetric contraction time in normal pregnancy and in pregnancy with placental vascular disease: the first clinical report using a new ultrasound technique.

OBJECTIVE: To study the fetal cardiac isovolumetric contraction time in normal and complicated pregnancies with placental vascular disease using a newly developed digital Doppler cardiography system. DESIGN: A preliminary case-control study. SETTING: Tertiary referral hospital. SAMPLE: One hundred and sixteen normal fetuses (20 to 40 weeks) and 55 complicated pregnancies with placental vascular disease as documented by a high systolic: diastolic ratio in the umbilical artery Doppler flow study. METHOD: A digital Doppler cardiography system with a high sampling rate (4,000 Hz) was used to detect the fetal cardiac valvular movements. The isovolumetric contraction time was measured as the interval between the mitral valve closing and the aortic valve opening with a built-in scale device. RESULTS: In normal pregnancy the isovolumetric contraction time remained remarkably constant with gestation and fetal heart rate. Comparison between clinical outcome and the isovolumetric contraction time of the complicated fetuses who were born within a week after the last determination of the isovolumetric contraction time revealed a strong correlation between prolonged isovolumetric contraction time duration and abnormalities in the perinatal course (non-reactive fetal heart rate pattern, low pulsatility index in the fetal middle cerebral artery Doppler flow and low birthweight infant). CONCLUSIONS: The isovolumetric contraction time is constant with gestation and fetal heart rate in normal pregnancy. In the presence of placental vascular disease a prolonged fetal isovolumetric contraction time predicts adverse outcome.

Case-Control Studies↗

PubMed1998

Inoperable pulmonary vascular disease in infants with congenital heart disease.

BACKGROUND: Among 120 infants less than 12 months of age who had lung biopsy and autopsy, 20 were inoperable because of severe irreversible pulmonary vascular disease. METHODS: The infants were classified into three groups. Group 1 comprised 6 patients who showed complete obstruction of the small pulmonary arterial lumen and atrophy of the peripheral arterial media and who were considered to have absolute operative contraindications. Group 2 comprised 6 patients who had no pathologic findings of absolute operative contraindication and had an index of pulmonary vascular disease of more than 2.2. They were isolated as having advanced plexogenic pulmonary arteriopathy. Group 3 comprised 8 patients who had extremely thickened media of small pulmonary arteries, with abnormally thickened media extending into the small peripheral arteries characterized by extremely narrow lumina and medial thickness exceeding luminal diameter. RESULTS: Six of the 9 patients in whom operative repair was abandoned on the basis of preoperative or intraoperative lung biopsy are still alive. Of the 11 patients who underwent operation without biopsy, none survived. CONCLUSIONS: Preoperative or intraoperative lung biopsy and assessment of arteriopathy based on the above criteria are recommended in all patients in whom fatal pulmonary vascular disease is suspected.

Atrophy↗

PubMed2006

Homocysteine metabolism, hyperhomocysteinaemia and vascular disease: an overview.

Hyperhomocysteinaemia has been regarded as a new modifiable risk factor for atherosclerosis and vascular disease. Homocysteine is a branch-point intermediate of methionine metabolism, which can be further metabolised via two alternative pathways: degraded irreversibly through the transsulphuration pathway or remethylated to methionine by the remethylation pathway. Both pathways are B-vitamin-dependent. Plasma homocysteine concentrations are determined by nongenetic and genetic factors. The metabolism of homocysteine, the role of B vitamins and the contribution of nongenetic and genetic determinants of homocysteine concentrations are reviewed. The mechanisms whereby homocysteine causes endothelial damage and vascular disease are not fully understood. Recently, a link has been postulated between homocysteine, or its intermediates, and an alterated DNA methylation pattern. The involvement of epigenetic mechanisms in the context of homocysteine and atherosclerosis, due to inhibition of transmethylation reactions, is briefly overviewed.

Animals↗

PubMed2002

Peripheral vascular disease risk factors among patients undergoing hemodialysis.

Peripheral vascular disease (PVD) is common among patients undergoing hemodialysis, but little is known regarding the risk factors for PVD in this population. Data from waves 1, 3, and 4 of the United States Renal Data System Dialysis Morbidity and Mortality Study were used to examine cross-sectional associations of a range of conventional cardiovascular risk factors and uremia- or dialysis-related variables with PVD. Univariate and multivariate logistic regression models were developed using wave 3 and 4 data. Odds ratios for the multivariate model derived using wave 3 and 4 data were then compared with those obtained with the wave 1 data set. For both data sets, PVD was positively associated with the duration of dialysis (vintage) and malnourished status and was negatively associated with serum albumin and parathyroid hormone levels and predialysis diastolic BP. Kt/V was negatively associated with PVD in waves 3 and 4 but not in wave 1. PVD was associated with increasing age, white (versus non-white) race, male gender, diabetes mellitus, coronary artery disease, cerebrovascular disease, smoking, and left ventricular hypertrophy, as for the general population, but not with hypertension or hyperlipidemia. In conclusion, PVD among hemodialysis patients is associated with both dialysis-specific variables and most conventional cardiovascular risk factors other than hypertension and hyperlipidemia. Future studies should prospectively examine the association of these variables identified in cross-sectional analyses with the de novo development of PVD in this population.

Aged↗

PubMed1995

Lupus anticoagulant in patients with peripheral vascular disease: a prospective study.

OBJECTIVE: To assess the incidence of lupus anticoagulant (LAC) in patients with peripheral vascular disease. DESIGN: Prospective clinical study. SETTING: University Hospital. MATERIALS: 20 patients with claudication (group 2), 20 patients with critical ischaemia (group 3) and 20 patients prior to elective abdominal aortic aneurysm surgery (group 4) were compared to 20 general surgical controls (group 1). CHIEF OUTCOME MEASURES: Venous blood samples for coagulation assay. MAIN RESULTS: Positive results for LAC by the Dilute Russell's viper venom time (DRVVT) with the platelet neutralisation procedure were present in 26 out of 60 vascular patients compared with none of the 20 general surgical controls. The three vascular groups showed a similar prevalence of LAC and this differed significantly from that in the control group (chi 2 = 10.94, p = 0.0009). Of the 26 positive results only three were associated with an abnormal activated partial thromboplastin time (APTT), which has previously been used as a marker for the presence of LAC activity. Fibrinogen levels were raised in seven of 20 patients in group 2 but were normal in the remaining vascular groups (p = 0.001). The mean factor VII level (124.1 units dl-1) in group 2 was higher than the mean of the remaining vascular patients (109.3 units dl-1, p < 0.05). CONCLUSIONS: The high prevalence of LAC in patients with peripheral vascular disease and the associated increased risk of early graft thrombosis may justify routine testing by DRVVT prior to reconstructive vascular surgery. Treatment of these patients with antiplatelet agents or formal anticoagulation perioperatively should be considered.

Aged↗

PubMed1975

Association of obliterative extracranial vascular disease with carotid sinus hyperaesthesia: a possible mechanism of transitory cerebral ischaemia.

In extensive studies of cerebral circulation it has been shown that obliterative extracranial vascular disease is associated with a particular regulatory pattern of cerebral circulation. In stenosis of the vertebral artery, of the internal carotid or in the subclavian steal syndrome, cerebral blood flow and O2 consumption was adequate under resting conditions and it is essentially the high cerebrovascular resistance which points to some derangement. The haemodynamic reserves of the brain being restricted, a sudden fall in heart rate may produce a significant decrease in the cerebral blood flow and thus bring about transitory cerebral ischaemic episodes. Twenty patients were studied in whom the production of transitory cerebral attacks was attributable to the coexistence of obliterative extracranial vascular disease and carotid sinus hypersensitivity. Elicitation of the carotid sinus reflex resulted in the production of transitory cerebral ischaemic spells together with a fall in cerebral blood flow in all cases. It is suggested that the transitory cerebral attacks are due in part of the cases to a coexistence of obliterative extracranial vascular disease and carotid sinus syncope. The majority of such patients become symptom-free if bradycardia or sinauricular or av block due to the carotid sinus hypersensitivity can be prevented by atropine therapy or pacemaker implantation.

Aged↗

PubMed1993

Transcutaneous ultrasonic imaging in peripheral vascular diseases.

Imaging is an important method for studying vascular disease particularly if combined with pulsed Doppler. The only situations where imaging alone may provide enough information to proceed with therapy is with aneurysmal disease and acute deep vein thrombosis. With these disorders, therapy is dependent on identifying the problem, its location, and extent. When occlusive arterial disease is the problem, the need for therapy will depend on the degree of narrowing. At the present time, transcutaneous ultrasonic imaging alone is not adequate to determine the degree of stenosis. Although there is no doubt that plaques can be seen on B-mode imaging, the extent to which they narrow the artery depends on an assessment of the flow velocity through the site of greatest narrowing. This can be determined by using a pulsed Doppler that permits selective sampling of flow from any point within the visualized arterial segment. While the procedure to be used will vary from one site to another within the arterial system, the basic principles are the same. The amount of velocity increase within a stenosis is related to the extent to which the diameter of the artery is reduced. The use of the duplex scanning method will permit an evaluation of both the arterial and venous systems at all sites accessible to this form of energy.

Aged↗

PubMed1954