Noninvasive diagnosis of ruptured peripheral atherosclerotic lesions and myocardial infarction by antibody profiling.

Novel biomarkers, such as circulating (auto)antibody signatures, may improve early detection and treatment of ruptured atherosclerotic lesions and accompanying cardiovascular events, such as myocardial infarction. Using a phage-display library derived from cDNAs preferentially expressed in ruptured peripheral human atherosclerotic plaques, we performed serological antigen selection to isolate displayed cDNA products specifically interacting with antibodies in sera from patients with proven ruptured peripheral atherosclerotic lesions. Two cDNA products were subsequently evaluated on a validation series of patients with peripheral atherosclerotic lesions, healthy controls, and patients with coronary artery disease at different stages. Our biomarker set was able to discriminate between patients with peripheral ruptured lesions and patients with peripheral stable plaques with 100% specificity and 76% sensitivity. Furthermore, 93% of patients with an acute myocardial infarction (AMI) tested positive for our biomarkers, whereas all patients with stable angina pectoris tested negative. Moreover, 90% of AMI patients who initially tested negative for troponin T, for which a positive result is known to indicate myocardial infarction, tested positive for our biomarkers upon hospital admission. In conclusion, antibody profiling constitutes a promising approach for noninvasive diagnosis of atherosclerotic lesions, because a positive serum response against a set of 2 cDNA products showed a strong association with the presence of ruptured peripheral atherosclerotic lesions and myocardial infarction.

Multicenter randomized controlled trial of the costs and effects of noninvasive diagnostic imaging in patients with peripheral arterial disease: the DIPAD trial.

OBJECTIVE: The purpose of our study was to compare the costs and effects of three noninvasive imaging tests as the initial imaging test in the diagnostic workup of patients with peripheral arterial disease. MATERIALS AND METHODS: Of 984 patients assessed for eligibility, 514 patients with peripheral arterial disease were randomized to MR angiography (MRA) or duplex sonography in three hospitals and to MRA or CT angiography (CTA) in one hospital. The outcome measures included the clinical utility, functional patient outcomes, quality of life, and actual diagnostic and therapeutic costs related to the initial imaging test during 6 months of follow-up. RESULTS: With adjustment for potentially predictive baseline variables, the learning curve, and hospital setting, a significantly higher confidence and less additional imaging were found for MRA and CTA compared with duplex sonography. No statistically significant differences were found in improvement in functional patient outcomes and quality of life among the groups. The total costs were significantly higher for MRA and duplex sonography than for CTA. CONCLUSION: The results suggest that both CTA and MRA are clinically more useful than duplex sonography and that CTA leads to cost savings compared with both MRA and duplex sonography in the initial imaging evaluation of peripheral arterial disease.

Serum C-reactive protein level is associated with abdominal aortic aneurysm size and may be produced by aneurysmal tissue.

BACKGROUND: Abdominal aortic aneurysms (AAA) are characterized by extensive transmural inflammation and C-reactive protein (CRP) has emerged as an independent risk factor for the development of cardiovascular disease. Therefore, we evaluated a possible association between serum CRP and aneurysm dimension in patients with asymptomatic AAA. Furthermore, the possibility of CRP production by aneurysmal tissue has been examined. METHODS AND RESULTS: Serum CRP was determined highly sensitive (hsCRP) and aneurysmal size was measured in 39 patients with AAA. The presence of CRP mRNA was assessed in the aneurysmal tissue of 16 patients. Mean (SD) hsCRP was 3.23 (2.96) mg/L. After log-transformation, hsCRP correlated significantly with aneurysmal size (r=0.477, P=0.002). When the patients were divided into 3 equally sized groups according to hsCRP level, aortic diameter increased from lowest to upper hsCRP-tertile (49 mm, 61 mm, and 67 mm, respectively; P<0.05 for 3rd versus 1st tertile). This association persisted after correction for risk factors. CRP mRNA was found in 25% of aneurysmal aortic tissues. CONCLUSIONS: This is the first report showing that serum hsCRP is associated with aneurysmal size and that-in at least some patients-CRP may be produced by aneurysmal tissue. These data underscore the inflammatory nature of AAA formation, suggesting that serum hsCRP may serve as a marker of AAA disease and that CRP produced in vascular tissue might contribute to aneurysm formation.

The effect of flow changes on the arterial system proximal to an arteriovenous fistula for hemodialysis.

Arterial remodeling in response to flow changes is controlled by the endothelium, sensing wall shear stress (SS) changes. The present study focuses on the remodeling capacities of the brachial (BA) and radial artery (RA) of 16 renal failure patients after arteriovenous fistula creation. Pre- and postoperatively at predetermined time-points, diameter, wall thickness and peak and mean SS were assessed. After arteriovenous fistula creation, acute increases in BA SS (p = 0.018) and lumen diameter (p = 0.028) were observed. The diameter further increased in the next year (p = 0.023), whereas BA SS remained unchanged. RA SS and diameter increased acutely (p = 0.005) and remained unaltered after 1 y. RA wall thickness tended to decrease acutely (p = 0.059) and increased steadily during 1 y (p = 0.008). BA and RA diameter acutely increased after an acute SS rise and remained augmented after 1 y. Also, the RA vessel wall thickness enlarged, indicating structural remodeling. After 1 y, however, these changes did not result in SS restoration.

Chlamydia pneumoniae serology is associated with thrombosis-related but not with plaque-related microembolization during carotid endarterectomy.

BACKGROUND AND PURPOSE: Chlamydia pneumoniae has repeatedly been associated with atherosclerotic disease. Our study was designed to clarify whether this association is based on C pneumoniae-induced transformation of a stable into an unstable atherosclerotic plaque or on stimulation of hypercoagulability leading to increased thrombotic arterial occlusions by C pneumoniae infection. Transcranial Doppler ultrasonographic monitoring of the middle cerebral artery during carotid endarterectomy offers the opportunity to study, before removal of the plaque, atherothrombotic emboli dislodging from an unstable carotid plaque (plaque-related emboli) and emboli related to (excessive) thrombus formation at the endarterectomy site after removal of the plaque and restoration of flow (thrombosis-related emboli). METHODS: C pneumoniae IgA (> or =1/16) and IgG (> or =1/64) seropositivity was assessed in 53 patients with symptomatic carotid artery disease undergoing carotid endarterectomy. The removed carotid plaques were studied histologically to assess plaque instability. RESULTS: Plaque- and thrombosis-related emboli were registered in 43 patients with an adequate transtemporal window. IgA seropositivity (58%) was associated significantly with thrombosis-related embolization (P=0.030) but not with plaque-related embolization or with histological plaque instability. CONCLUSIONS: C pneumoniae serology is associated with microembolization after endarterectomy and restoration of flow. Since these microemboli represent platelet aggregations and are related to cerebrovascular complications, our data suggest that C pneumoniae infection contributes to cerebrovascular events in patients with carotid artery disease through stimulation of thrombosis.

Chlamydia pneumoniae serology: comparing a commercial enzyme immunoassay and microimmunofluorescence test in patients with cardiovascular disease.

Chlamydia pneumoniae has been associated with cardiovascular disease and the detection of C. pneumoniae antibodies has subsequently challenged many cardiovascular investigators. The micro-immunofluoresence (MIF) test is considered the gold standard for detection of C. pneumoniae antibodies, but requires a high-level of expertise for adequate interpretation. We compared an enzyme immunoassay (EIA) with a microimmunofluorescence test for the detection of C. pneumoniae IgG- and IgA antibodies in sera of 141 patients with atherosclerosis. The MIF test was read by two independent observers. The interobserver agreement of the MIF test for detection of seropositivity at various cut-off levels was good for IgG and for IgA. The intra-test agreement of the EIA was excellent for IgG and IgA. The agreement between EIA and MIF in detection of IgG- and IgA antibodies was adequate at low but not at high titer levels. At low titer levels, the sensitivity, specificity, positive and negative predictive value of EIA compared to the MIF test was sufficient. The sensitivity of the EIA increased, improving the agreement with the MIF at high titer levels by retesting sera with elevated titers at higher pre-dilutions. In conclusion, the EIA shows sufficient agreement with the MIF test in the detection of C. pneumoniae seropositivity. Therefore, the EIA is a practical alternative to the MIF in the detection of C. pneumoniae antibodies in patients with cardiovascular disease, bearing in mind that the sensitivity of the EIA depends on the antibody titer.

Comparison of contrast-enhanced magnetic resonance angiography and digital subtraction angiography in patients with chronic critical ischemia and tissue loss.

RATIONALE AND OBJECTIVES: To compare the ability of intra-arterial digital subtraction angiography (IA-DSA) and total runoff contrast-enhanced magnetic resonance angiography (CE-MRA) to demonstrate peripheral arterial anatomy, specifically in patients with chronic critical ischemia and tissue loss. MATERIALS AND METHODS: Twenty-three consecutive patients with chronic critical ischemia and tissue loss underwent CE-MRA and IA-DSA within 2 days. Two teams, consisting of an interventional radiologist and vascular surgeon who were blinded to each other's results, determined the number of named arteries (21 segments) and the presence of >/=50% stenosis or occlusion. RESULTS: Compared with IA-DSA, both teams detected significantly more arterial segments with CE-MRA, both above and below the knee (team 1: above knee 7.0 versus 5.2, P = 0.002, and below knee 8.5 versus 5.4, P < 0.001; team 2: above knee 7.1 versus 5.4, P = 0.004, and below knee 8.3 versus 5.9, P < 0.001). Interobserver agreement between the 2 teams with regard to presence of arteries and the presence of stenoses and/or occlusions yielded kappa values of 0.76 (95% confidence interval 0.71-0.81) for IA-DSA and 0.73 (95% confidence interval 0.66-0.80) for CE-MRA. Treatment was changed based on the CE-MRA findings in 8/23 (35%) patients. CONCLUSIONS: In the present study CE-MRA detected more patent arteries than IA-DSA in patients with chronic critical ischemia and tissue loss. CE-MRA can modify the choice of therapeutic strategy in these patients.

Shear stress depends on vascular territory: comparison between common carotid and brachial artery.

Shear stress (SS) is thought to be constant throughout the vascular system. Evidence for this supposition is scarce, however. To verify this hypothesis in vivo, we assessed common carotid (CCA) and brachial artery (BA) peak and mean wall shear rate (SR) noninvasively in 10 healthy volunteers (23.7 +/- 3.4 yr) with an ultrasound SR estimation system. SS was estimated from SR and calculated whole blood viscosity. SR was higher (P < 0.05) in the CCA (mean: 359 +/- 111 s(-1); peak: 1,047 +/- 345 s(-1)) than in the BA (mean: 95 +/- 24 s(-1); peak: 770 +/- 170 s(-1)). Whole blood viscosity was higher in the BA than in the CCA (5.1 +/- 0.7 vs. 3.3 +/- 0.6 mPa. s; P < 0.001). Peak SS did not differ between the CCA and the BA, whereas mean SS was significantly higher in the CCA (1.15 +/- 0.21 Pa) than in the BA (0.48 +/- 0.15 Pa; P < 0.001). These results demonstrate that BA SS strongly deviates from CCA SS in vivo.

Brachial artery shear stress is independent of gender or age and does not modify vessel wall mechanical properties.

The objective of the present study was to obtain brachial artery (BA) baseline shear stress (SS) values in healthy volunteers and to relate this to gender and age. Peak and mean wall shear rate (SR) were noninvasively measured in 30 healthy subjects using an SR estimation system. Arterial diameter and wall characteristics were obtained with a wall tracking system. SS was estimated from SR and calculated whole blood viscosity. Intrasubject variability and the effects of age and gender were assessed. Intrasubject variability of BA peak and mean SR were 16.2% and 28.6%. Baseline peak ( approximately 3.0 +/- 0.7 Pa) and mean SS ( approximately 0.5 +/- 0.2 Pa) were not gender-dependent, nor were they influenced by age. No vessel wall parameter related to BA SS. No differences in BA SS were observed between the genders and no influence of age was apparent. Our results indicate that the BA adequately responds to chronic changes in blood flow.

Diagnosis of abdominal aortic hypoplasia by state-of-the-art MR angiography.

Abdominal aortic hypoplasia is a rare vascular variant with possible major clinical sequelae when the renal arteries are also involved. The condition is thought to result from embryonic overfusion of the two dorsal aortas. The diagnosis may be considered in patients presenting with hypertension in the neonatal period and severely reduced or absent arterial pulses in the groin. We present contrast-enhanced state-of-the-art magnetic resonance angiography imaging findings in an 8-year-old boy with abdominal aortic hypoplasia.

Synergistic effect of Toll-like receptor 4 and CD14 polymorphisms on the total atherosclerosis burden in patients with peripheral arterial disease.

BACKGROUND: Genes involved in the regulation of immune responses, such as Toll-like receptor 4 (TLR4) and CD14, show genetic variations with potential functional implications. Because atherosclerosis is an inflammatory process apparently modulated by chronic infections, we studied the effect of single nucleotide polymorphisms (SNPs) in TLR4 and CD14 on the extent of clinically relevant atherosclerosis in patients with peripheral arterial disease (PAD). METHODS: Using an in-house-developed polymerase chain reaction-based restriction length polymorphism assay, we determined the genotype, allele frequency, and carrier traits of the TLR4 +896 A>G and the CD14 -260 C>T SNPs in 607 white Dutch patients with PAD. The extent of clinically relevant atherosclerosis was determined on the basis of the number of vascular territories involved, ie, coronary, cerebral, aortic, and peripheral. RESULTS: A total of 55% of the patients had PAD only. Approximately one third of the patients had two and 11% had three vascular territories affected by clinically relevant atherosclerosis. The TLR4 +866 G allele frequency was 11%, and the CD14 -260 T allele frequency was approximately 74%. Among PAD patients, TLR4 +896 G allele carriership was univariantly associated with extensive (more than two vascular territories affected) atherosclerotic disease (odds ratio, 2.22; P = .020; chi(2) test), whereas CD14 -260 C>T carriership/homozygosity was not. Trend analysis showed that the TLR4 +866 G allele frequency increased with the number of vascular territories affected by clinically relevant atherosclerosis (P trend, .0074). In a multivariate logistic regression analysis including cardiovascular risk factors and TLR4 and CD14 SNPs, only the interaction variable "TLR4 +896 G allele carriership/CD14 -260 TT genotype" survived as an independent predictor of extensive atherosclerotic disease (P = .031; odds ratio, 4.2; 95% confidence interval, 1.1-15.4). CONCLUSIONS: The carrier trait TLR4 G allele/CD14 TT genotype, rather than each SNP individually, is associated with the extent of clinically relevant atherosclerotic disease. Considering the importance of immune responses in atherogenesis and the genetic variation of immune regulatory genes, our data provide an explanation for interindividual differences in susceptibility to atherosclerosis and demonstrate the need to take a wider approach in analyzing relevant carrier traits instead of individual polymorphisms in relation to atherosclerosis.

Endothelin-1 levels and conduit artery mechanical properties in end-stage renal disease.

BACKGROUND: Endothelial cell (EC) dysfunction markers are increased in end-stage renal disease (ESRD). The present study focused on the relationship between EC markers, conduit artery wall mechanics and hemodynamics in ESRD. METHODS: In 29 ESRD patients and 16 controls, brachial artery diameter, distension, and wall thickness was measured and circumferential wall stress (CWS) calculated. Shear stress was determined with a shear rate-estimating system. Furthermore, von Willebrand factor antigen (vWF) and endothelin-1 (ET-1) levels were measured. RESULTS: vWF (p = 0.002) and ET-1 (p < 0.001) were higher in ESRD patients and vWF was related to ET-1 (r = 0.70, p = 0.005). Peak (p = 0.001) and mean shear stress (p = 0.003) were significantly lower in ESRD patients, and ET-1 showed an inverse log linear relation with both (peak: r = -0.59, p = 0.016; mean: r = -0.64, p = 0.007). Also, ET-1 was log linearly related to CWS (r = 0.58, p = 0.014). CONCLUSION: These results indicate that, in ESRD, conduit artery shear stress is lower, which might be secondary to an increased peripheral vascular resistance caused by higher ET-1 levels.

C-reactive protein in peripheral arterial disease: relation to severity of the disease and to future cardiovascular events.

BACKGROUND: Serum C-reactive protein (CRP) has proven to be an independent marker of the extent of atherosclerosis in patients with coronary, cerebrovascular, and peripheral arterial disease. In this prospective observational study, we wanted to assess the relationship between serum CRP and extent of disease transversely and longitudinally in time, as well as future cardiovascular complications in patients with peripheral arterial disease (PAD). Hypothesizing that CRP not only is a marker of but also actively participates in atherogenesis, we explored the possibility of CRP production by femoral atherosclerotic plaques. METHODS: Serum CRP was measured as highly sensitive (hsCRP) in 387 patients with PAD attending the vascular clinic of a university and 2 affiliated teaching hospitals. Serum hsCRP was related to the ankle-brachial pressure index (ABPI) as an indication of severity of disease at inclusion and at 12 months' follow-up and to future events (death and coronary, cerebral, and peripheral arterial events). In femoral plaques, the production of CRP was analyzed with reverse transcription-polymerase chain reaction, and CRP plaque localization was assessed with immunostaining on serial tissue sections with antibodies toward CRP, smooth muscle cells, T cells, and macrophages. RESULTS: The hsCRP (average +/- SD) was 3.26 +/- 2.41 mg/L. Serum hsCRP showed a correlation with baseline and 12-month follow-up ABPI (Spearman rank correlation; P < .05 for both correlations). When the patients were divided into three equally sized groups according to baseline serum hsCRP, the ABPI at baseline and at 12 months decreased significantly from the low- to the high-hsCRP group (baseline ABPI: 0.70, 0.65, and 0.57, P < .01; 12-month follow-up ABPI: 0.78, 0.70, and 0.65, P < .01). These associations persisted after correction for conventional risk factors. Furthermore, serum hsCRP was related to the combined end point "death and/or any cardiovascular event" (log-rank test; P = .04) during a median 24-month follow-up period. Reverse transcription-polymerase chain reaction analysis showed CRP production in 4 of 14 femoral plaques. CRP was detected in all femoral plaques, but not in healthy brachial arteries. Immunoreactivity for CRP was observed in smooth muscle cells, macrophages, and T cells. CONCLUSIONS: Serum hsCRP was related to the severity of PAD, showing a relation to future hemodynamic function and cardiovascular events in PAD patients. In addition to coronary plaques, aneurysmal aortas, and failed venous coronary bypasses, femoral plaques also produce CRP, thus illustrating that the production of CRP may represent a universal response to vascular injury and suggesting that vascular CRP may contribute to plaque development.

Prosthetic femorocrural bypass surgery and adjuvant arteriovenous fistulae.

The use of an adjuvant arteriovenous fistula (AVF) in vascular procedures is controversial. The purpose of this study was to evaluate our experience with this adjunct in femorodistal bypass surgery. Patients who received a prosthetic femorocrural bypass with or without an AVF were studied (n = 56). Risk factors, Doppler and plethysmographic characteristics, and preoperative angiograms were analyzed. Of all prosthetic bypasses anastomosed to a single crural vessel, 75% received an AVF (AVF+, n = 44) whereas 25% did not (AVF-, n = 12). Preoperative ankle/brachial pressures and angiographic outflow scores in both groups were comparable. Successful revascularization doubled ankle/brachial pressure indices and tripled toe pressures. Bypasses with a maximum angiographic outflow score performed better than those with low scores (p <0.05). The overall patency rates after 1, 12, and 24 months were 87%, 62%, and 47%, respectively; an AVF did not influence these numbers although a trend favoring the use of a fistula was present at 1 year (AVF-, 54% vs. AVF+, 64%; p = 0.11). Moreover, 2-year limb salvage was not different between groups (AVF-, 75% vs. AVF+, 68%). The use of an AVF in prosthetic femorodistal bypass surgery does not improve rates of patency and limb salvage in the long term.

Hemodynamics of venous cuff interposition in prosthetic arteriovenous fistulas for hemodialysis.

PURPOSE: The durability of prosthetic arteriovenous fistulas (AVF) for hemodialysis is jeopardized by thrombotic occlusions due to intimal hyperplastic stenoses. In arterial reconstructive surgery, peripheral arterial bypasses with prosthetic material benefit from a venous cuff at the distal anastomosis. Therefore, a study was performed to assess the effect of a venous cuff at the venous anastomosis of PTFE graft AVFs in terms of stenosis development, hemodynamics and patency rates. METHODS: A subset of 40 patients from a multicenter study were enrolled into the study, of which 20 patients were randomized for venous cuff interposition. Duplex measurements to detect stenoses and volume flows were performed at 6, 12, 26 and 52 weeks postoperatively. Relative distension (RD) and wall shear rate (WSR) were calculated by means of vessel wall Doppler tracking (VWDT). RESULTS: The total number of stenoses was significantly less in the cuff group (21 vs. 33; p = 0.045). This feature was found at the site of the venous anastomosis (cuff 5; no cuff 12). Volume flow, graft and efferent vein diameters, RD and WSR in the graft and efferent vein were comparable for both groups. WSR in the venous anastomosis tended to be lower in the cuff group (768 vs. 1,448 s(-1), p = 0.068). Volume flows and WSR were significantly lower in failing grafts. Patency rates were similar in both groups (primary patency 13 vs. 29%; secondary patency 78 vs. 67%). CONCLUSIONS: A venous cuff at the venous anastomosis of PTFE graft AVFs results in less stenoses, but improved patency rates could not be demonstrated.

Comparison of treatment plans for peripheral arterial disease made with multi-station contrast medium-enhanced magnetic resonance angiography and duplex ultrasound scanning.

OBJECTIVE: This study was undertaken to investigate the effects of substituting multi-station total outflow contrast medium-enhanced magnetic resonance angiography (CE-MRA) for color duplex ultrasound (US) scanning on treatment planning in the diagnostic workup of patients with suspected or known peripheral arterial occlusive disease. Patients and methods One hundred consecutive patients referred because of suspected or proved peripheral arterial occlusive disease to a University Hospital underwent both aortoiliac duplex US scanning and multi-station total outflow CE-MRA. For 73 of these patients (57% men; mean age, 62 years) treatment or treatment plans could be retraced. Eighteen patients also underwent femoro-popliteal duplex US scanning. Three experienced vascular surgeons retrospectively formulated two sets of treatment plans based on standardized clinical parameters and either duplex US scanning or CE-MRA. The main outcome measure was proportion of patients for whom the treatment plan matched actual treatment without additional use of intra-arterial digital subtraction angiography. Actual treatment, based on all available information, including results of duplex US scanning, CE-MRA, and any other diagnostic tests, served as the standard of reference. RESULTS: Duplex US scanning provided enough information for treatment planning in 46, 45, and 53 patients versus 67, 68, and 66 patients when CE-MRA was used (surgeons 1, 2, and 3, respectively; surgeons 1 and 2, P <.001; surgeon 3, P =.007). Treatment plans based on duplex US scanning exactly matched actual treatment in 37 of 73 patients (51%; surgeon 1), 36 of 73 patients (49%; surgeon 2), and 46 of 73 patients (63%; surgeon 3). Treatment plans based on CE-MRA exactly matched actual treatment in 56 of 73 patients (77%; surgeon 1), 55 of 73 patients (75%; surgeon 2), and 51 of 73 patients (70%; surgeon 3). Positive predictive value and negative predictive value of duplex US scanning as measures of ability to discriminate between surgical and nonsurgical treatment were 0 of 0 (undefined) and 43 of 46 (93%), 1 of 2 (50%) and 40 of 43 (93%), and 5 of 5 (100%) and 44 of 48 (92%) for surgeons 1, 2, and 3, respectively. For CE-MRA, positive and negative predictive values were 11 of 13 (85%) and 50 of 54 (93%), 10 of 12 (83%) and 51 of 56 (91%), and 8 of 13 (62%) and 48 of 53 (91%), respectively, for surgeons 1, 2, and 3. CONCLUSION: Compared with aorto-iliac and femoro-popliteal duplex US scanning, multi-station total outflow CE-MRA is more effective for treatment planning in most patients with known or suspected peripheral arterial occlusive disease.

Vasculin, a novel vascular protein differentially expressed in human atherogenesis.

Recent suppressive subtractive hybridization analysis on human atherosclerotic plaque-derived RNA revealed genes upregulated in plaques with a thrombus versus stable plaques. Clone SSH6, containing part of a putative open reading frame of an unknown protein, was further investigated. Full-length cDNA, coding for a 473-amino acid (aa) protein, was identified in a vascular smooth muscle cell (SMC) cDNA library. Bioinformatics suggested the presence of multiple SSH6 variants due to alternative splicing of exon 3. Multiple-tissue Northern blot analysis demonstrated a differential expression pattern of these variants, as a ubiquitously expressed SSH6 mRNA missing exon 3, was detected apart from a putative vascular SMC-specific form containing exon 3. Western blot analysis indicated a ubiquitous 35-kDa protein (SSH6-beta), in addition to a 45-kDa protein (vasculin), detected in the vascular wall and in plasma. Analysis of arteries displaying various stages of atherosclerosis indicated that the vasculin/SSH6-beta ratio increases throughout atherogenesis. Immunohistochemical analysis demonstrated cytoplasmic expression of SSH6 gene products in macrophages, endothelial cells, and SMCs. In summary, we identified a novel mRNA/protein, vasculin, in the arterial wall and plasma. The regulated expression of vasculin in plaques suggests a role in atherogenesis. Moreover, its presence in plasma opens perspectives for vasculin as a marker for atherosclerosis.