Increasing echogenicity of diffuse circumferential thickening ("macaroni sign") of the carotid artery wall with decreasing inflammatory activity of Takayasu arteritis.

We report a case of sonographic follow-up showing brightening of the diffuse circumferential thickening (halo) of the carotid artery wall (the so-called "macaroni sign") in a patient with decreasing inflammatory activity of Takayasu arteritis over a 6-month period. Sonographic follow-up in patients with Takayasu arteritis may be a useful complementary tool for evaluation of inflammatory activity. Besides a reduction of halo diameter, an increase in wall echogenicity appears to be a sign of decreasing inflammation.

Human urinary kininogenase reduces the endothelial injury by inhibiting Pyk2/MCU pathway.

The injury of endothelial cells is one of the initiating factors in restenosis after endovascular treatment. Human urinary kallidinogenase (HUK) is a tissue kallikrein which is used for ischemia-reperfusion injury treatment. Studies have shown that HUK may be a potential therapeutic agent to prevent stenosis after vascular injury, however, the precise mechanisms have not been fully established. This study is to investigate whether HUK can protect endothelial cells after balloon injury or H2O2-induced endothelial cell damage through the proline-rich tyrosine kinase 2 (Pyk2)/mitochondrial calcium uniporter (MCU) pathway. Intimal hyperplasia, a decrease of pinocytotic vesicles and cell apoptosis were found in the common carotid artery balloon injury and H2O2-induced endothelial cell damage, Pyk2/MCU was also up-regulated in such pathological process. HUK could prevent these injuries partially via the bradykinin B2 receptor by inhibiting Pyk2/MCU pathway, which prevented the mitochondrial damage, maintained calcium balance, and eventually inhibited cell apoptosis. Furthermore, MCU expression was not markedly increased if Pyk2 was suppressed by shRNA technique in the H2O2 treatment group, and cell viability was significantly better than H2O2-treated only. In short, our results indicate that the Pyk2/MCU pathway is involved in endothelial injury induced by balloon injury or H2O2-induced endothelial cell damage. HUK plays an protective role by inhibiting the Pyk2/MCU pathway in the endothelial injury.

Segment-specific genetic effects on carotid intima-media thickness: the Northern Manhattan study.

BACKGROUND AND PURPOSE: Carotid intima-media thickness (IMT) is a surrogate marker of subclinical atherosclerosis and a strong predictor of stroke and myocardial infarction. The object of this study was to determine the association between carotid IMT and 702 single nucleotide polymorphisms in 145 genes. METHODS: B-mode carotid ultrasound was performed among 408 Hispanics from the Northern Manhattan Study. The common carotid artery IMT and bifurcation IMT were phenotypes of interest. Genetic effects were evaluated by the multivariate regression model adjusting for traditional vascular risk factors. For each individual, we calculated a gene risk score (GRS) defined as the total number of the significant single nucleotide polymorphisms in different genes. Subjects were then divided into 3 GRS categories using the 2 cutoff points: mean GRS +/-1 SD. RESULTS: We identified 6 significant single nucleotide polymorphisms in 6 genes for common carotid artery IMT and 7 single nucleotide polymorphisms in 7 genes for bifurcation IMT using the probability value of 0.005 as the significant level. There were no common significant genes for both phenotypes. The most significant genes were the tissue plasminogen activator (P=0.0005 for common carotid artery IMT) and matrix metallopeptidase-12 genes (P=0.0004 for bifurcation IMT). Haplotype analysis did not yield a more significant result. Subjects with GRS >or=9 had significantly increased IMT than those with GRS

Platelet deposition in rabbit common carotid arteries promoted by arterial stenosisand spasm. A quantitative and morphological study.

Coronary arteriograhy in patients with ischemic heart disease often shows spasm of the coronary arteries. The question is whether spasm is a triggering factor for thrombosis in a stenotic artery. If so, what are the mechanisms for this? A stenosing teflon ring was applied to the right common carotid artery of anesthetized rabbits and 1-nor-epinephrine was dripped over the outer surface of both carotid arteries, causing spasm. In control animals an indifferent solution did not cause spasm. Nineteen rabbits were killed 30 min or 24 h after treatment. Microscopically, arteries with stenosis and spasm contained thrombi nearby the stenosis significantly more often than arteries in control animals. In another 14 rabbits, killed at 30 min, the number of platelets on the intimal surface away from the stenosis was quantified. In arteries with both stenosis and spasm the counts were significantly greater than in arteries with no treatment. The intimal surface in stenotic and spastic arteries showed assumed imprints of eddying flow and endothelial injury downstream and upstream of the stenosis. Spastic arteries showed increased folding of the internal elastic membrane, altered endothelial cells, and adhering platelets. Spasm in a rabbit artery with a preformed stenosis facilitates thrombosis probably by creating increased flow disturbances. Spasm may induce endothelial injury, causing adherence of platelets.

The effect of temporary aneurysm clip on the common carotid artery of atherosclerotic rabbits.

BACKGROUND: We compared the effect of temporary aneurysm clips on atherosclerotic and nonatherosclerotic CCA of rabbits by morphometric and ultrastructural methods. METHODS: The rabbits (N = 12) were divided into 2 groups: the first group was fed a 2% cholesterol diet, and the second group, a normal diet for 4 weeks. Atherosclerotic lesions developed after 4 weeks. Temporary aneurysm clips were placed on the left CCA of both groups; the right CCA of both groups served as control. Thus, a total of 4 groups were used: atherosclerotic (A), atherosclerotic/clip (AC), nonatherosclerotic (NA), and nonatherosclerotic/clip (NAC). Temporary aneurysm clips were applied for 1, 5, and 10 minutes in the AC and NAC groups. No temporary clip was placed on the right CCA (A and NA groups). The affected parts of the CCA via clips were examined under light microscope and SEM. RESULTS: Comparison of atherosclerotic and nonatherosclerotic CCA of rabbits under light microscope indicated that the wall of atherosclerotic CCA was thicker than that of nonatherosclerotic CCA. The difference between the thickness of atherosclerotic and nonatherosclerotic CCAs was significant. SEM analyses showed that in nonatherosclerotic CCAs, the effect of temporary aneurysm clips was seen after 10 minutes, but in atherosclerotic CCAs, the effect was seen within the 1st minute of clipping and continued in the 5th and 10th minutes. CONCLUSION: The duration of temporary clipping should be decreased for the neurovascular surgery of atherosclerotic patients.

Characteristics and baseline clinical predictors of future fatal versus nonfatal coronary heart disease events in older adults: the Cardiovascular Health Study.

BACKGROUND: Although >80% of annual coronary heart disease (CHD) deaths occur in adults aged >65 years and the population is aging rapidly, CHD event fatality and its predictors in the elderly have not been well described. METHODS AND RESULTS: The first myocardial infarction (MI) or CHD death among the 5888 adults aged > or =65 years occurring during enrollment in the Cardiovascular Health Study during 1989-2001 was identified and adjudicated. Characteristics measured at examinations before the event were examined for associations with case fatality (death before hospitalization or hospital discharge) and for differences in predictors by demographics or clinical history. During a median follow-up of 8.2 years, 985 CHD events occurred, of which 30% were fatal. Case fatality decreased slightly over time, ranging from 28% to 30% per year in the early 1990s versus 23% by 2000-2001; with adjustment for age at MI and gender, there was a 6% lower odds of fatality with each successive year (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.90 to 0.98). Case fatality was similar by race and gender but higher with age and prior CHD (MI, angina, or revascularization). When considered alone, many subclinical disease measures, such as common carotid intima-media thickness, ankle-arm index, left ventricular mass by ECG, and a major ECG abnormality, and traditional risk factors, such as diabetes and hypertension, were associated with fatality. In multivariable analysis, independent predictors of fatality were prior congestive heart failure (OR, 3.20; 95% CI, 2.32 to 4.41), prior CHD rather than only history of MI (OR, 2.51; 95% CI, 1.84 to 3.43), diabetes (OR, 1.66; 95% CI, 1.10 to 2.31), and age (OR, 1.21 per 5 years; 95% CI, 1.07 to 1.37), adjusted for gender and each other. Prior congestive heart failure, regardless of left ventricular systolic function, age, gender, or prior CHD, conferred a > or =3-fold increased risk of fatality in almost all subgroups. CONCLUSIONS: Among community-dwelling older adults, CHD case fatality remains substantial, with easily identifiable risk factors that may be different from those that predict incident disease. In the elderly in whom the risk/benefit of therapies may be influenced by multiple competing comorbidities and care needs, risk stratification possibly may be improved further by focusing more aggressive care on specific patients, especially those with a history of congestive heart failure or prior CHD.

High resolution imaging of the fibrous microstructure in bovine common carotid artery using optical polarization tractography.

The biomechanical properties of artery are primarily determined by the fibrous structures in the vessel wall. Many vascular diseases are associated with alternations in the orientation and alignment of the fibrous structure in the arterial wall. Knowledge on the structural features of the artery wall is crucial to our understanding of the biology of vascular diseases and the development of novel therapies. Optical coherence tomography (OCT) and polarization-sensitive OCT have shown great promise in imaging blood vessels due to their high resolution, fast acquisition, good imaging depth, and large field of view. However, the feasibility of using OCT based methods for imaging fiber orientation and distribution in the arterial wall has not been investigated. Here we show that the optical polarization tractography (OPT), a technology developed from Jones matrix OCT, can reveal the fiber orientation and alignment in the bovine common carotid artery. The fiber orientation and alignment data obtained in OPT provided a robust contrast marker to clearly resolve the intima and media boundary of the carotid artery wall. Optical polarization tractography can visualize fiber orientation and alignment in carotid artery.

Cytokine polymorphisms associated with carotid intima-media thickness in stroke patients.

BACKGROUND AND PURPOSE: Carotid intima-media thickness (IMT) reflects generalized atherosclerosis and is predictive of future vascular events. Evidence exists that carotid IMT is heritable, and genetic studies can provide clues in the pathogenesis of atherosclerosis. METHODS: We recruited 470 white ischemic stroke patients, measured common carotid artery (CCA) IMT, and analyzed 54 polymorphisms with suspected roles in atherosclerosis. RESULTS: Among the polymorphisms tested, the angiotensin-converting enzyme insertion/deletion, osteopontin (OPN) T-443C, monocyte chemoattractant protein-1 (MCP-1) G-927C, and MCP-1 A-2578G polymorphisms were associated with CCA-IMT in age-gender-adjusted analysis. In multivariate analysis, the association between the OPN and MCP-1 polymorphisms remained significant. The OPN-443C allele was associated with increased IMT in the dominant model (0.053 mm for the TC and CC genotypes; P=0.001). The MCP-1-927C allele was associated with increased IMT in the additive model (0.040 mm for each C allele; P=0.001), and the MCP-1-2578 G allele was associated with decreased IMT in the recessive model (0.088 mm for the GG genotype; P=0.002). CONCLUSIONS: The OPN and MCP-1 genes, coding for 2 cytokines with known roles in atherosclerosis, may contribute to increased carotid IMT and warrant further study.

Transendothelial migration of ferric ion in FeCl3 injured murine common carotid artery.

INTRODUCTION/OBJECTIVES: Adventitial application of FeCl(3) causes endothelial injury, platelet aggregation, and a rapid onset of thrombus formation. The transmigration pathway of the ferric ion has not been definitively identified. Using a combination of TEM and X-ray elemental analysis, this study aims to elucidate the endothelial pathway of ferric ion migration in carotid artery. METHODS AND RESULTS: Vascular injury was induced by placing a Whatman #1 filter paper strip saturated with 10% FeCl(3) over the common carotid artery in male C57BL/6 mice for 3 min. After rinsing in saline, the mice were terminated at 10 or 30 min. The FeCL(3) exposed segments of the common carotid artery were dissected, and processed for TEM. Thrombus formation was observed in all cases. Endothelial and smooth muscle injuries were observed in segments of the vessel in direct contact with the oxidant. The endothelial injury ranged from minimal damage to total denudation. The basal endothelial surface adjacent to the internal elastic lamina showed accumulation of electron opaque vesicles. The membrane enclosed particles transmigrated across the endothelium and exocytosed into the lumen. The nature of the particles shown by STEM/EDS was rich in ferric ion. Elemental analysis also showed that some ferric oxide aggregates formed near the developing thrombus in the vascular lumen. CONCLUSION: Our results showed the ferric ion permeated the endothelial basal lamina before entering the arterial lumen via endocytic-exocytic pathway. This study provides an ultrastructural framework for future analysis of the adluminal and luminal injuries in this model.

Asymptomatic carotid atherosclerosis is associated with circulating chlamydia pneumoniae DNA in younger normotensive subjects in a general population survey.

OBJECTIVE: Chlamydia pneumoniae infection has been associated with atherosclerosis, but serodiagnosis is unreliable in predicting vascular infection. Direct detection of circulating chlamydial DNA in peripheral blood mononuclear cells (PBMCs) was thus evaluated as a marker for cardiovascular risk in a general population survey using the common carotid intima-media thickness (IMT) as surrogate marker of asymptomatic atherosclerosis. METHODS AND RESULTS: C pneumoniae DNA in PBMCs was determined by nested polymerase chain reaction and associated with IMT for 1032 healthy participants of a general population survey who were within the highest or lowest IMT distribution quartile. C pneumoniae DNA was more prevalent in those with increased IMT (13.4% versus 10.7%), but this was not significant in univariate and of borderline significance in multivariate analysis. Testing for potential effect modifications by known strong determinants of an increased IMT in group interaction analysis revealed an independent association between C pneumoniae DNA and IMT in normotensive subjects (odds ratio [OR], 2.06; 95% CI, 1.05 to 4.03; P=0.04) and in those <70 years old (OR, 1.84; 95% CI, 1.06 to 3.19; P=0.03). CONCLUSIONS: Asymptomatic atherosclerosis is associated with circulating C pneumoniae DNA independently of classical cardiovascular risk factors in normotensive subjects and those <70 years old. C pneumoniae has been implicated in atherogenesis. We determined the association of chlamydial DNA in peripheral blood mononuclear cells with the carotid intima-media thickness from 1032 healthy subjects from a general population survey. A stratified group interaction analysis revealed an independent association in normotensive subjects and those <70 years old.

The 5-hydroxytryptamine2A receptor antagonist sarpogrelate hydrochloride inhibits acute platelet aggregation in injured endothelium.

In this study, the effect of sarpogrelate hydrochloride, a 5-hydroxytryptamine2A receptor antagonist, on platelet aggregation at the site of injured carotid artery endothelium was examined. The rat common carotid artery was clamped for 30 min to induce endothelial injury. Sarpogrelate hydrochloride was administered before and after the injury, and the effects were compared with those in rats receiving sham operation only and those receiving clipping injury but no sarpogrelate hydrochloride. The animals were killed 24 h after the procedure. The common carotid artery was examined by scanning electron microscopy and stained immunochemically for factor VIII. Sarpogrelate hydrochloride treatment was associated with reduced aggregation of platelets on electron microscopy and lower expression of factor VIII at the injured intima. Sarpogrelate hydrochloride has an inhibitory effect on platelet aggregation at the intima in the acute stage after injury, suggesting that this drug may be used to prevent early ischaemic complications after surgical or endovascular arterial intervention.

Systemic lupus erythematosus: an independent risk factor for endothelial dysfunction in women.

BACKGROUND: Systemic lupus erythematosus (SLE) patients have a significantly increased risk of coronary heart disease (CHD) that is not fully explained by classic risk factors. Endothelial dysfunction is an early stage in the process of atherogenesis. Our aim was to determine whether endothelial dysfunction occurs in SLE and whether it is associated with the occurrence of classic Framingham risk factors. METHODS AND RESULTS: We studied 62 women with SLE (1997 revised criteria) and 38 healthy women. Demographic and risk factor data were collected. In patients, disease activity and treatment-related parameters were also assessed. Endothelial function was assessed by flow-mediated dilation (FMD) in the brachial artery in response to reactive hyperemia. Carotid intima-media thickness (IMT) and the presence of carotid plaques were also assessed in SLE patients. FMD was impaired in SLE patients (median, 3.6%; range, -6.3% to 13.7%; versus median, 6.9%; range, -6.6% to 17.8%, P<0.01). Using multiple regression analysis that included all subjects in which we retained all the classic CHD risk factors, we found that systolic blood pressure (P=0.019) and SLE (P=0.017) were significantly associated with impaired FMD. Within SLE patients, IMT showed a negative correlation with percent FMD (r=-0.37, P<0.01). In stepwise multiple regression of SLE patients only that also included SLE factors and IMT, IMT alone was independently associated with FMD (P=0.037). CONCLUSIONS: Patients with SLE have endothelial dysfunction that remained significant even after adjustment for other classic CHD risk factors. Within SLE patients, endothelial dysfunction correlates negatively with IMT, another marker of early atherosclerosis. Understanding the mechanism(s) of endothelial dysfunction in SLE may suggest novel strategies for CHD prevention in this context.

Estradiol accelerates reendothelialization in mouse carotid artery through estrogen receptor-alpha but not estrogen receptor-beta.

BACKGROUND: The atheroprotective effect of 17beta-estradiol (E(2)) has been suggested in women and clearly demonstrated in animals through both an effect on lipid metabolism and a direct effect on the cells of the arterial wall. It has been shown, for example, that E(2) promotes endothelium-dependent relaxation and accelerates reendothelialization in rats. Similar studies have been undertaken in mice to appreciate the molecular mechanism of this process. METHODS AND RESULTS: We report here a model of electric carotid injury adapted from that described by Carmeliet et al (1997) that allows us to precisely evaluate the reendothelialization process. We demonstrate that E(2) accelerates endothelial regeneration in castrated female wild-type mice. In ovariectomized transgenic mice in which either the estrogen receptor (ER)-alpha or ERbeta gene has been disrupted, E(2) accelerated reendothelialization in female ERbeta knockout mice, whereas this effect was abolished in female ERalpha knockout mice. CONCLUSIONS: This study demonstrates that ERalpha but not ERbeta mediates the beneficial effect of E(2) on reendothelialization and potentially the prevention of atherosclerosis.

Cytokine-induced mobilization of circulating endothelial progenitor cells enhances repair of injured arteries.

BACKGROUND: The existence of circulating endothelial progenitor cells (CEPCs) has previously been documented. These cells can be mobilized by cytokines and are recruited to sites of injury, where they may participate in tissue repair. In the present study, we examined the hypothesis that mobilization of CEPCs by exogenous granulocyte-colony stimulating factor (G-CSF) enhances repair of injured arteries by facilitating reendothelialization and inhibiting neointima development. METHODS AND RESULTS: Male rats were injected daily with 50 microg/kg recombinant human G-CSF or 0.9% NaCl SC for 8 days. On the fifth day of treatment, 1 mL of blood was collected for fluorescence-activated cell sorting analysis of mononuclear cells, and the animals underwent balloon angioplasty of the common carotid artery. The animals were killed at 2 or 4 weeks after injury, and the carotid arteries were harvested and processed for immunohistochemistry, scanning electron microscopy (SEM), and morphometric analysis of endothelialization and neointimal formation. G-CSF increased the number of circulating mononuclear cells that express endothelial cell lineage markers several-fold. SEM and immunohistochemical staining with the endothelial marker, platelet and endothelial cell adhesion molecule-1, showed rapid and nearly complete (>90%) reendothelialization of the denuded vessels in the G-CSF-treated animals compared with <20% in the control animals. Reendothelialization was paralleled by a decrease in inflammation in the vessel wall. Neointima thickness was reduced by approximately 60% in the G-CSF-treated animals compared with control animals at 2 and 4 weeks after injury. CONCLUSIONS: We postulate that cytokine-induced mobilization of CEPCs may be a suitable therapeutic strategy for prevention of restenosis after revascularization procedures.

Alimentary lipemia, postprandial triglyceride-rich lipoproteins, and common carotid intima-media thickness in healthy, middle-aged men.

BACKGROUND: Alimentary lipemia has been associated with coronary heart disease and common carotid artery intima-media thickness (IMT). This study was designed to investigate the relations of subclasses of postprandial triglyceride-rich lipoproteins (TRLs) with IMT. METHODS AND RESULTS: Ninety-six healthy 50-year-old men with an apolipoprotein (apo) E3/E3 genotype underwent an oral fat tolerance test and B-mode carotid ultrasound examination. The apo B-48 and apo B-100 contents of each fraction of TRLs were determined as a measure of chylomicron remnant and VLDL particle concentrations. In the fasting state, LDL cholesterol (P<0.05) and basal proinsulin (P<0. 05) were significantly related to IMT, whereas HDL cholesterol, plasma triglycerides, and insulin were not. In the postprandial state, plasma triglycerides at 1 to 4 hours (P<0.01 at 2 hours), total triglyceride area under the curve (AUC) (P<0.05), incremental triglyceride AUC (P<0.01), and the large VLDL (Sf 60 to 400 apo B-100) concentration at 3 hours (P<0.05) were significantly related to IMT. Multivariate analyses showed that plasma triglycerides at 2 hours, LDL cholesterol, and basal proinsulin were consistently and independently related to IMT when cumulative tobacco consumption, alcohol intake, waist-to-hip circumference ratio, and systolic blood pressure were included as confounders. CONCLUSIONS: These results provide further evidence for postprandial triglyceridemia as an independent risk factor for early atherosclerosis and also suggest that the postprandial triglyceridemia is a better predictor of IMT than particle concentrations of individual TRLs.

Bronchial hyperresponsiveness to methacholine is associated with increased common carotid intima-media thickness in men.

BACKGROUND: Respiratory alterations have been associated with subsequent coronary heart diseases in numerous population-based studies. The underlying mechanisms remain largely unknown. The objective of this study was to examine the association between bronchial hyperresponsiveness (BHR) to methacholine (which reflects local inflammation in the bronchus) and common carotid intima-media thickness (CCA-IMT). METHODS AND RESULTS: As part of the European Community Respiratory Health Survey follow-up, in Paris Center, we assessed BHR to methacholine (> or =20% decrease in FEV1 for a maximum methacholine dose of 4 mg) and measured CCA-IMT by ultrasonography in 255 adults free of cardiovascular diseases aged 29 to 56 years (123 men, 132 women; mean age 44.5 years, 43.5% never smokers). In men, CCA-IMT mean value was higher in subjects with BHR than in those without (0.68+/-0.11 versus 0.62+/-0.09 mm, P=0.002). No association was found in women. Multivariate analysis confirmed the independent association between BHR and CCA-IMT in men (adjusted odds ratio for a 0.10-mm increase in CCA-IMT=2.1, 95% confidence interval: 1.1 to 4.3; P=0.02). These results remained similar after exclusion of asthmatic subjects (n=11). In each strata of smoking status (nonsmoker, ex-smoker, and current smokers), CCA-IMT mean values tended to be higher in subjects with BHR than in those without, although the difference between the 2 groups was more pronounced in current smokers. CONCLUSIONS: The results of the present study suggest that BHR is independently associated with CCA-IMT in men. The interrelationships between cardiovascular and respiratory alterations should be further investigated.

A pilot study into measurements of markers of atherosclerosis in periodontitis.

BACKGROUND: Periodontitis may be a possible risk factor for atherosclerosis. The current pilot study explored arterial wall thickness and other variables associated with atherosclerosis in healthy subjects with and without periodontitis. METHODS: Patients with moderate (N = 34) and severe periodontitis (N = 15) and controls (N = 14) were recruited. Intima media thickness (IMT) of the common carotid arteries (CCA), internal carotid arteries (ICA), and bifurcations of carotid arteries (BCA) was estimated bilaterally using B-mode ultrasound. An overall IMT was calculated as the mean of these six measurements. C reactive protein (CRP), fibrinogen, and von Willebrand factor (vWf) were measured in plasma as indicators of systemic inflammation and atherosclerotic disease. Microalbuminuria was determined as a marker of endothelial cell dysfunction. RESULTS: IMT for CCA were 0.64, 0.68, and 0.69 mm for control, moderate, and severe periodontitis, respectively (not significant). IMT for BCA did not vary among groups. IMT of ICA was largest for severe periodontitis (0.81 mm); corresponding values for controls and moderate periodontitis were 0.58 and 0.55 mm, respectively (P= 0.023). Severe periodontitis patients had an overall IMT of 0.76 mm, while moderate periodontitis patients and controls had lower values (0.64 and 0.65 mm, respectively; P= 0.153). After adjusting for potential confounding factors, the increased IMT for ICA in severe periodontitis was also significant (Padj = 0.040). CRP (P= 0.020, Padj = 0.050) and vWf (P= 0.019, Padj = 0.013) were higher in periodontitis than controls; microalbuminuria was not different between groups. Power calculations suggest that a 4-fold expansion of the severe patient and control groups will result in a high chance (power level 80%) that a clinically significant association between the overall IMT and periodontitis will be observed. CONCLUSION: The present pilot study indicates that a full study investigating the relationship between periodontitis and atherosclerosis is warranted.

Insulin resistance and carotid atherosclerosis in 221 patients with potential hyperglycemia.

OBJECTIVE: To investigate the relationship between insulin resistance and carotid atherosclerosis in patients with potential hyperglycemia. METHODS: A total of 221 patients were recruited among those with potential hyperglycemia. All participants underwent physical examination, medical history interview, and 75 g oral glucose tolerance test. Venous blood was sampled for measurement of insulin and cholesterol levels. The intima-media thickness (IMT) in bilateral common carotid arteries was observed by B-mode ultrasound. Insulin resistance index was calculated by homeostasis model assessment (HOMA-IR). Subjects were stratified in quintiles according to HOMA-IR values. Risk factors and atherosclerotic parameters were analyzed. RESULTS: With HOMA-IR value increase, incidence of impaired glucose tolerance, diabetes mellitus, hypertension, and coronary artery disease increased, the levels of triglyceride (TG), low density lipoprotein cholesterol (LDL-C), fasting plasma glucose, 2 hour plasma glucose, and fasting insulin increased as well, while the level of high density lipoprotein cholesterol (HDL-C) decreased. Meanwhile, all atherosclerotic parameters increased. Multivariate regression analysis showed that TG, total cholesterol, HDL-C, LDL-C levels, and ln(HOMA-IR) were related to IMT, hence were risk factors for IMT increase. CONCLUSION: Insulin resistance is implicated in atherogenesis.

Mechanical properties and structure of carotid arteries in mice lacking desmin.

OBJECTIVE: Our aim was to determine in desmin homozygous mutant mice the viscoelastic properties, the mechanical strength and the structure of the carotid artery. METHODS: To assess the viscoelastic properties of large arteries, we have performed an in vivo analysis of the diameter-, and distensibility-pressure curves of the common carotid artery (CCA) in homozygous (Des -/-), heterozygous (Des +/-) and wild-type (Des +/+) mice. To evaluate the mechanical strength, we have measured the in vitro intraluminal pressure producing the rupture of the carotid artery wall. The structure analysis of the arterial wall was based on histology and electronic microscopy. RESULTS: A lower distensibility and an increase of arterial wall viscosity were observed in Des -/- compared with Des +/+. Arterial thickness of Des -/- was similar to those of Des +/+, without changes in elastin and collagen contents. Electron microscopy revealed that the perimeter of cellular fingerlike-projections was smaller in Des -/-, indicating that the cells have lost part of their connections to the extracellular matrix. The rupture pressure was significantly lower in Des -/- (1500+/-200 mmHg) compared with Des +/+ (2100+/-80 mmHg) indicating a lower mechanical strength of the vascular wall. No significant difference was found between Des +/- and Des +/+. CONCLUSION: The desmin is essential to maintain proper viscoelastic properties, structure and mechanical strength of the vascular wall.

A novel S-nitrosothiol causes prolonged and selective inhibition of platelet adhesion at sites of vascular injury.

OBJECTIVE: Platelet adhesion to areas of endothelial denudation following angioplasty is an important factor contributing to the limitations of this technique. Lipophilic S-nitrosothiols like S-nitroso-N-valerylpenicillamine (SNVP) are novel nitric oxide (NO) donor drugs with anti-platelet and vasodilator properties that are selective for areas of endothelial denudation. Here we assess the inhibitory effect of SNVP on platelet adhesion to angioplastied rabbit carotid arteries. METHODS: A rabbit model was used to measure adhesion of radiolabelled platelets to carotid arteries following balloon angioplasty. The effects of SNVP were compared to the conventional NO donor, nitroglycerin (NTG). Electron microscopy was used to visualize adhering platelets. RESULTS: Angioplasty resulted in endothelial denudation with only a modest reduction in vessel contractility. In vivo administration of NTG and SNVP (both 200 nmol) prevented the hyper-aggregability (approximately 20%) of circulating platelets caused by angioplasty. However, bolus NTG failed to inhibit adhesion of radiolabelled platelets 30 min after angioplasty, despite inducing a transient 30% reduction in systemic blood pressure. In contrast, equimolar SNVP had little effect on blood pressure but markedly inhibited platelet adhesion (62% compared to control; P=0.003). Platelet adhesion was confirmed with electron microscopy. CONCLUSION: The prolonged effects of SNVP at sites of endothelial damage suggest that novel S-nitrosothiols might offer a means of targeted delivery of an antiplatelet agent to areas of vascular injury.