Edge vascular response after polymer-free vs. polymer-based paclitaxel-eluting stent implantation.

BACKGROUND: It is unknown if lack of polymer can provoke a different edge response in drug-eluting stents. The aim of this study was to compare edge vascular response between polymer-free paclitaxel-eluting stent (PF-PES) and polymer-based paclitaxel-eluting stents (PB-PES). METHODS AND RESULTS: A total of 165 eligible patients undergoing percutaneous coronary intervention were prospectively randomized 1:1 to receive either PF-PES or PB-PES. Those patients with paired intravascular ultrasound (IVUS) after procedure and at 9-month follow-up were included in this analysis.Seventy-six patients with 84 lesions, divided into PB-PES (38 patients, 41 lesions) and PF-PES groups (38 patients, 43 lesions) had paired post-procedure and 9-month follow-up IVUS and were therefore included in this substudy. There was a significant lumen decrease at the proximal edge of PF-PES (from 9.02±3.06 mm(2)to 8.47±3.05 mm(2); P=0.040), and a significant plaque increase at the distal edges of PF-PES (from 4.39±2.73 mm(2)to 4.78±2.63 mm(2); P=0.004). At the distal edge there was a significant plaque increase in the PF-PES compared to PB-PES (+8.0% vs. -0.6%, respectively; P=0.015) with subsequent lumen reduction (-5.2% vs. +6.0%, respectively; P=0.024). CONCLUSIONS: PF-PES had significant plaque increase and lumen reduction at the distal edge as compared to PB-PES, probably due to difference in polymer-based drug-release kinetics between the 2 platforms.

Randomized comparison between polymer-free versus polymer-based paclitaxel-eluting stent: two-year final clinical results.

BACKGROUND: Most drug-eluting stents currently in use are coated with a polymer carrying the drug that is released for several weeks. However, a durable polymer may provoke hypersensitive reaction, delayed artery healing, and eventually stent thrombosis. The aim of this study was to investigate the safety and efficacy of a polymer-free paclitaxel-eluting stent (PF-PES) versus a polymer-based PES (PB-PES). METHODS AND RESULTS: Eligible patients undergoing percutaneous coronary intervention were randomized 1:1 to receive either PF-PES or PB-PES. The primary end point was late loss at 9 months. Intravascular ultrasound analysis at 9 months and final 2-year clinical follow-up were also performed. From October 2007 to April 2009, 164 patients were enrolled and randomized into 2 groups (PF-PES: n = 84; PB-PES: n = 80). Mean in-stent lumen loss was 0.90 ± 0.59 mm for PF-PES and 0.49 ± 0.52 mm for PB-PES (P < 0.001). Mean neointimal area by intravascular ultrasound was higher in PF-PES than in PB-PES (1.42 ± 1.09 versus 0.51 ± 0.61 mm(2); P < 0.001). At 2 years, a composite end point of all-cause death, any myocardial infarction, and target vessel revascularization occurred in 36.9% for PF-PES and 16.3% for PB-PES (P = 0.004), mainly driven by a higher rate of target vessel revascularization (PF-PES: 35.7%; PB-PES: 13.8%; P = 0.001). One late stent thrombosis was observed in PF-PES. CONCLUSIONS: Compared with PB-PES, PF-PES was associated with increased neointimal proliferation and subsequent clinical restenosis. Polymer plays an essential role in the performance of drug-eluting stents. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01375855.

Qualitative and quantitative accuracy of ultrasound-based virtual histology for detection of necrotic core in human coronary arteries.

The aim was to test the accuracy of virtual histology (VH) for detecting necrotic core (NC) in an ex vivo human model of coronary arteries as compared to real histology (RH). A total of nine consecutive explanted hearts were included in the study. Coronary segments, clearly identified by anatomical landmarks, were analyzed by intravascular ultrasound (IVUS-VH) immediately after heart collection and thereafter by RH. NC was expressed as absolute (total amount) and relative (corrected for plaque area) values. Correlation analysis was performed using linear regression models at cross-section level, with correction for repeated measurements per patient, and at segment level. Receiver operator curves (ROC) were developed for testing accuracy of VH in detecting RH-NC. Overall, 321 mm were analyzed corresponding to 642 IVUS-VH frames and corresponding histological slices. VH and RH-NC areas were 0.24 ± 0.43 and 0.16 ± 0.43 mm(2), respectively (p < 0.001). At cross-section level, the correlation between VH and RH-NC was moderate in absolute (r = 0.50, p < 0.001) and poor in relative values (r = 0.43, p = 0.120). At the segment level, this correlation improves in terms of absolute values (r = 0.80, p = 0.01), but was not significant in terms of relative values (r = 0.43, p = 0.25). The ROC curve showed a C-statistics of 0.904 (p < 0.001) with high sensitivity (94 %), but low specificity (53 %) and low positive predictive value (48 %). Although VH has a high sensitivity in identifying RH-NC, it has a low specificity and low positive predictive value. In addition, it is not able to accurately quantify its size within the corresponding histological specimen.

Endothelial and smooth muscle cells dysfunction distal to recanalized chronic total coronary occlusions and the relationship with the collateral connection grade.

OBJECTIVES: This study sought to assess the vascular function in patients with chronic total coronary occlusions (CTO) immediately after successful percutaneous recanalization and its relation with the pre-existing collateral circulation. BACKGROUND: CTOs represent a long-acting occlusion of a coronary vessel, in which the progressively developed collateral circulation may limit ischemia and symptoms. However, it is unknown if the coronary segment distal to the occlusion has a preserved vascular function. METHODS: We prospectively enrolled 19 consecutive patients, after percutaneous coronary intervention of a CTO. Luminal diameter, measured by quantitative coronary angiography, and coronary blood flow at level of epicardial coronary artery distal to the treated CTO was assessed before and after administration of acetylcholine (Ach), adenosine, and nitroglycerin (NTG). Collaterals were assessed angiographically by grading of Rentrop and of collateral connections (CC1: threadlike continuous connection; CC2: side branch-like connection). RESULTS: Overall, Ach and adenosine caused coronary artery vasoconstriction (p=0.001 and p=0.004, respectively), whereas NTG failed to induce vasodilation (p=0.084). Coronary blood flow significantly decreased with Ach (p=0.005), significantly increased with NTG (p=0.035), and did not change with adenosine (p=0.470). Patients with CC2 collaterals (n=8) had less vasoconstriction response and reduction in coronary blood flow after Ach (p=0.005 and p=0.008, respectively), and better vasomotor response to NTG (p=0.029) than patients with CC1 collaterals (n=11). CONCLUSIONS: Significant endothelial and smooth muscle dysfunction is present in the distal segments of successfully recanalized CTOs, and that seems to be more pronounced in the presence of a low grading of collateral circulation.

Adequate antiplatelet regimen in patients on chronic anti-vitamin K treatment undergoing percutaneous coronary intervention.

AIM: To investigate the impact of dual antiplatelet therapy (DAT) in patients on anti-vitamin K (AVK) regimen requiring percutaneous coronary intervention (PCI). METHODS: Between February 2006 and February 2008, 138 consecutive patients under chronic AVK treatment were enrolled in this registry. Of them, 122 received bare metal stent implantation and 16 received drug eluting stent implantation. The duration of DAT, on top of AVK treatment, was decided at the discretion of the clinician. Adequate duration of DAT was defined according to type of stent implanted and to its clinical indication. RESULTS: The baseline clinical characteristics of patients reflect their high risk, with high incidence of comorbid conditions (Charlson score ≥ 3 in 89% of the patients). At a mean follow-up of 17 ± 11 mo, 22.9% of patients developed a major adverse cardiac event (MACE): 12.6% died from cardiovascular disease and almost 6% had an acute myocardial infarction. Major hemorrhagic events were observed in 7.4%. Adequate DAT was obtained in only 44% of patients. In the multivariate analysis, no adequate DAT and Charlson score were the only independent predictors of MACE (both P = 0.02). CONCLUSION: Patients on chronic AVK therapy represent a high risk population and suffer from a high MACE rate after PCI. An adequate DAT regimen and absence of comorbid conditions are strongly associated with better clinical outcomes.

Emergent versus elective percutaneous stent implantation in the unprotected left main: long-term outcomes from a single-center registry.

BACKGROUND: Unprotected left main (ULM) coronary disease is considered by contemporary guidelines a class I indication for surgery. However, percutaneous coronary intervention (PCI) is often carried out in the ULM in either emergent or high-risk elective procedures. The aim of this study was to evaluate ULM-PCI as a feasible and safe procedure in the emergent setting, and to analyze outcomes in both scenarios. METHODS: Angiographic and clinical data were collected retrospectively for all patients who underwent emergent or elective PCI on ULM at our center from January 2006 to June 2009. All patients were followed up with a clinical visit or telephone interview. Main outcomes included major adverse cardiac events (MACE) and its individual components: cardiac death, myocardial infarction (MI) and target lesion revascularization. These were analyzed at the longest follow-up available. RESULTS: A total of 98 consecutive patients with significant LM disease were included. Fifty-seven of them were treated as a planned procedure (elective group) and 41 as an emergent procedure (emergent group). Procedural success was achieved in 100% of cases in the elective group and in 88% of the emergent group (p = 0.011). Higher use of drug-eluting stents (DES) was recorded in the elective group (75% versus 45% in the emergent group; p <0.002). The emergent group presented a higher in-hospital mortality (24% versus 2% in the elective group; p <0.001). At a mean follow-up of 626 ± 380 days, the overall MACE rate was similar betweeen the two groups (23% in the emergent group versus 17% in the elective group; p = 0.52). Independent predictors of MACE after discharge follow-up were postprocedure minimal diameter and DES use. CONCLUSIONS: Emergent PCI of the ULM exhibits worse in-hospital outcomes as compared to elective procedures. However, after discharge, long-term outcomes remain comparably good between groups.

The Guideliner™ catheter for stent delivery in difficult cases: tips and tricks.

INTRODUCTION: Stent delivery in complex coronary anatomy with severe calcification and tortuosity is still a common cause of percutaneous coronary interventions (PCI) failure. Recently, a new support rapid exchange catheter, the Guideliner, has been designed specifically for device delivery. METHODS: From June 2010 to December 2010, we performed 10 cases using the Guideliner catheter to improve backup support and facilitate stent delivery: 2 emergent PCI for ST elevation myocardial infarction, and 8 stable elective PCI. In 3 cases the operator chose the femoral access, in 2 cases crossover from radial to femoral access was needed, and the other cases were performed radially. In 2 cases PTCA with drug-eluting balloon was performed; in the other cases second-generation drug-eluting stent was implanted. RESULTS: One case, the first one, failed, as stent could not be delivered to the target lesion. The other 9 cases were performed successfully. Three proximal dissections were detected and sealed with stent implantation. In 2 cases, we had stent damage due to the passage of the stent through the Guideliner metal collar. Another stent had to be used. CONCLUSIONS: In our experience, the Guideliner catheter is safe to use and helps device delivery in difficult settings. We describe here our experience with the Guideliner catheter for stent delivery and backup support; we discuss its utility and drawbacks in acute and stable clinical settings. Moreover, the aim of this article is to help interventional cardiologists using the device in difficult lesions to avoid potential complications.

Utilidad del catéter Tornus ® en las oclusiones coronarias crónicas no dilatables / Usefulness of the Tornus ® catheter in nondilatable coronary chronic total occlusion

El tratamiento percutáneo de las oclusiones coronarias crónicas (OCC) representa un desafío. La segunda causa del fracaso de la técnica es la imposibilidad de dilatarlas con un balón. Describimos nuestra experiencia con el nuevo catéter Tornus® (Asahi Intecc; Aichi, Japón), diseñado específicamente para facilitar el tratamiento de OCC «no dilatables». Desde noviembre de 2008 hasta marzo de 2010, hemos tratado a 17 pacientes (media de edad, 62 años; el 88% varones, el 82% dislipémicos, el 52% hipertensos, el 29% diabéticos) en los que no se consiguió dilatar la lesión con ningún catéter balón tras haber cruzado la lesión con una guía de angioplastia. El catéter se utilizó con éxito en 15 casos, sin complicaciones, y se consiguió finalizar la revascularización del vaso. Durante el seguimiento clínico (mediana, 573 días), no se registraron eventos de importancia. El uso del catéter Tornus® es seguro y factible en las OCC de lesiones previamente no dilatables de manera convencional (AU)

The treatment of coronary chronic total occlusions (CTO) remains a challenge for the interventional cardiologist. Failure of balloon angioplasty is the second more common cause of an unsuccessful procedure. We describe our experience with the use of the new Tornus® catheter (Asahi Intecc, Aichi, Japan) designed specifically for the treatment of “nondilatable” CTO. Between November 2008 and March 2010, 17 patients (age 62 years, 88% men, 82% dyslipidemia, 52% hypertension, 29% diabetes) were treated in whom balloon dilatation had failed after crossing the lesion with the guide. The use of Tornus® catheter was successful without complications in 15. All patients underwent clinical follow-up (median, 573 days) with no documented major adverse events. The use of the Tornus® catheter is safe and feasible in those patients with CTO lesions in whom balloon angioplasty has been unsuccessful (AU)

[Usefulness of the Tornus® catheter in nondilatable coronary chronic total occlusion]. / Utilidad del catéter Tornus(®) en las oclusiones coronarias crónicas no dilatables.

The treatment of coronary chronic total occlusions (CTO) remains a challenge for the interventional cardiologist. Failure of balloon angioplasty is the second more common cause of an unsuccessful procedure. We describe our experience with the use of the new Tornus® catheter (Asahi Intecc, Aichi, Japan) designed specifically for the treatment of "nondilatable" CTO. Between November 2008 and March 2010, 17 patients (age 62 years, 88% men, 82% dyslipidemia, 52% hypertension, 29% diabetes) were treated in whom balloon dilatation had failed after crossing the lesion with the guide. The use of Tornus® catheter was successful without complications in 15. All patients underwent clinical follow-up (median, 573 days) with no documented major adverse events. The use of the Tornus® catheter is safe and feasible in those patients with CTO lesions in whom balloon angioplasty has been unsuccessful.

[Rescue maneuver for entrapped stent in the coronary tree]. / Maniobra para rescate de stent atrapado en el árbol coronario.

We describe two patients in whom stents dislodged from the unexpanded balloon during angioplasty and remained trapped in the coronary tree. In one patient the stent was located in the curvature of the circumflex artery and, in the other patient, it was detected in the distal left main artery. Retrieval of the undeployed stents was accomplished in the first case after advancing a low profile balloon through the stent and, in the second case, after placing a second guidewire exterior to the stent. In both cases, the balloon was inflated distally and the stents were dislodged after pulling the balloon back towards the guiding catheter and then withdrawing the whole system.

Maniobra para rescate de stent atrapado en el árbol coronario / Rescue maneuver for entrapped stent in the coronary tree

Describimos el caso de dos pacientes que durante la angioplastia los stents se desprendieron del balón sin expandir y quedaron atrapados en el árbol coronario. En un paciente el stent quedó enclavado en la curvatura de la arteria circunfleja y en el otro paciente en el tronco común distal. Los stents se extrajeron en el primer caso tras avanzar un balón de bajo perfil a través del stent y en el otro tras colocar otra guía exterior al stent y situar un balón distal. En ambos casos se hinchó el balón distal a los stents y se logró desenclavar al retirar el balón hacia el catéter guía y después todo el sistema.

We describe two patients in whom stents dislodged from the unexpanded balloon during angioplasty and remained trapped in the coronary tree. In one patient the stent was located in the curvature of the circumflex artery and, in the other patient, it was detected in the distal left main artery. Retrieval of the undeployed stents was accomplished in the first case after advancing a low profile balloon through the stent and, in the second case, after placing a second guidewire exterior to the stent. In both cases, the balloon was inflated distally and the stents were dislodged after pulling the balloon back towards the guiding catheter and then withdrawing the whole system.

Endothelial progenitor cell capturing stent and short dual antiplatelet therapy in patients on chronic anti-vitamin k regimen undergoing percutaneous coronary interventions: long-term outcomes of a single centre registry.

AIMS: To evaluate outcomes of the endothelial progenitor cell (EPC) capture stent in patients on chronic anti-vitamin K (AVK) regimen, requiring percutaneous coronary intervention (PCI). METHODS AND RESULTS: Between February 2007 and February 2008, 78 consecutive patients under chronic AVK treatment undergoing PCI were enrolled in the registry and received an EPC capture stent. The incidence of comorbid conditions was analysed by the Charlson index. Dual antiplatelet therapy (DAT, aspirin and clopidogrel) was prescribed for one month only together with the AVK treatment, after PCI. Major adverse clinical events (MACE) rate, included death, acute myocardial infarction (MI) or target lesion revascularisation (TLR), incidence of stent thrombosis and rate of haemorrhagic events were collected. A?Charlson index >3 was present in 89% of patients. At 14±8 months the cumulative rate of MACE was 22%: 10 deaths (six cardiac deaths), and six TLR. No MI or definitive/probable stent thromboses occurred during follow-up. Four major haemorrhagic episodes occurred during follow-up, all of them after the first month. CONCLUSIONS: Patients on AVK treatment represent a highly comorbid population with a high event rate after PCI. The strategy of PCI with an EPC capture stent and short duration of DAT may be used in patients who need a short-term DAT.

Diabetes mellitus: a prothrombotic state implications for outcomes after coronary revascularization.

Coronary stent thrombosis is a serious problem in the drug-eluting stent era. Despite aggressive antiplatelet therapy during and after percutaneous coronary intervention (PCI), the incidence of sub-acute stent thrombosis remains approximately 0.5%-2%, which may represent a catastrophic clinical situation. Both procedural factors and discontinuation of antiplatelet therapy are normally associated with this event. We report on simultaneous stent thromboses of two drug-eluting stents implanted in two different vessels, which resulted in a life-threatening clinical condition. Possible contributing factors that led to synergistic thrombotic effects are discussed.

Left main coronary artery stenosis following surgical valve replacement: changing valvular into ischemic heart disease.

Left main stem coronary artery (LMSCA) stenosis after surgical aortic valve replacement (AVR) is a rare but potentially lethal complication. Among the different possible causes, antegrade cardioplegia for direct coronary perfusion seems to be the most significant and prevalent. Here we discuss two cases of late presentation of iatrogenic coronary ostial stenosis following valve replacement surgery. Both cases were successfully treated with percutaneous intervention and stent implantation.

Plaque vulnerability and related coronary event prediction by intravascular ultrasound with virtual histology: "it's a long way to tipperary"?

Identification of so-called "vulnerable plaque" or "high-risk" plaques have spawned manifold attempts to develop diagnostic tools capable to afford this task. This task is particularly challenging but the reward is high: local intervention on identified "vulnerable plaque" could preclude plaque thrombosis and possibly prevent acute coronary syndromes. Various imaging techniques are currently under investigation by extensive clinical testing to identify which could become the most sensible and specific modality for vulnerable plaque detection. Noninvasive techniques are fascinating for their easily applicability to a broad population but nowadays are not sufficiently powered for this task. The emerging technologies with the greatest resolution are indeed catheter-based and many intravascular modalities have been developed for identification of "vulnerable plaque". Among these, IVUS-Virtual Histology (IVUS-VH) is the most promising technique in the field. IVUS-VH offers an in vivo opportunity to assess plaque morphology and histology. IVUS-VH uses underlying frequency information along with echoes intensity, while grey-scale IVUS data are obtained from echoes of different intensity or amplitude. The major advantage of IVUS-VH is that it is based on a device that is practical for use in the clinical setting and that it generates a real-time assessment of plaque morphology. Unfortunately, numerous challenging issues still need to be overcome until the numerous "vulnerable plaques" could be identified and successfully treated. Future efforts may identify plaques that are on a trajectory of evolution toward a vulnerable state, and help us target interventions to those plaques most likely to develop plaque disruption and related complications.

Engineering aspects of stents design and their translation into clinical practice.

The implantation of coronary stents is a relevant part of interventional procedures for percutaneous revascularization. The wide acceptance of coronary stenting was based on the results of two highly significant trials which have shown the superiority of stenting over balloon angioplasty in terms of reduction of angiographic restenosis and need for repeated intervention in focal lesions and large coronary arteries. Since then, the growing use of stent market was impressive. A rapidly increasing number of different stent type with different material and designs has been introduced in the market both for bare metal stent and drug eluting stent. This review will summarize the different components of stent design that are important in term of biological response of the arterial wall and clinical outcome. In addition, new stent platforms, mainly represented by the biodegradable stent will be shortly reviewed since it may provide in the near future a more "physiological" answer to stent implantation, reducing vascular injury and accelerating vessel healing with consequent improving in clinical outcome.

Decreased plasma adiponectin concentration in major depression.

Adiponectin is the most abundant adipose-derived plasma protein. Recently adiponectin levels have been linked to most variables of metabolic syndrome and conventional risk factors for cardiovascular disease. However, its relation with major depression is yet unclear. We evaluated plasma adiponectin levels in 32 first-episode drug-naïve major depression (DSM-IV-TR) patients without conventional risk factors for cardiovascular disease and 32 matched healthy subjects. Major depression patients displayed lower adiponectin plasma levels compared to controls (P<0.01). Adiponectin significantly correlated with depression severity, as assessed by HAM-D (rho=0.83, P<0.001). This study shows decreased plasma adiponectin concentrations in major depression patients and relates adiponectinemia reduction to major depression severity.

Association between enhanced soluble CD40 ligand and proinflammatory and prothrombotic states in major depressive disorder: pilot observations on the effects of selective serotonin reuptake inhibitor therapy.

OBJECTIVE: Major depressive disorder (MDD) is associated with low-grade inflammation, and it is considered a risk factor for coronary artery disease (CAD). CD40 ligand (CD40L) plays an important role in inflammation, platelet activation, and clotting system activation. We investigated soluble CD40L (sCD40L) expression in MDD and assessed whether it may represent a molecular mechanism that links inflammation and a prothrombotic state and whether this condition may be modified by selective serotonin reuptake inhibitor (SSRI) therapy. METHOD: Levels of sCD40L, interleukin-1beta (IL-1beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), soluble P-selectin (sP-selectin), activated factor VII (FVIIa), and prothrombin fragment 1+2 (F1+2) were measured in 46 drug-naïve, first-episode MDD patients without conventional CAD risk factors and in 46 matched healthy controls. Participants were screened between March 2002 and November 2005. Twenty of the 46 MDD patients were then randomly assigned to either sertraline 100 mg/day (N = 10) or citalopram 20 mg/day (N = 10); the aforementioned variables were measured at baseline and after 6 weeks of treatment. RESULTS: Compared with control subjects, MDD patients had higher baseline levels of sCD40L, IL-1beta, IL-6, TNF-alpha, sP-selectin, FVIIa, and F1+2. In the clinical group, sCD40L levels, HAM-D total scores, and proinflammatory markers were strongly intercorrelated. In contrast, there were no significant correlations in the control group. Mood improvement achieved with SSRI therapy was associated with significant reduction in sCD40L, proinflammatory markers, and prothrombotic markers expression. (All p values < .0001.) CONCLUSIONS: This pilot study shows that CD40/ CD40L pathway up-regulation in MDD patients relates increased levels of sCD40L to a prothrombotic state and, preliminarily, indicates that SSRI therapy may significantly reduce sCD40L and CD40L levels associated with proinflammatory and prothrombotic states.

Regulatory role of endothelium in the expression of genes affecting arterial calcification.

Vascular calcification is a highly regulated process sharing features of bone mineralization. Since endothelium regulates many of the processes during atherogenesis, we monitored the expression of genes involved in calcification upon exposure of human coronary artery endothelial cells (HCAECs) to atherogenic stimuli. Genes studied were: core binding factor alpha-1 (Cbfa1/Runx2), a pivotal transcriptional regulator of osteogenesis; bone morphogenetic protein-2 (BMP2), an inducer of cartilage and bone; and matrix gla-protein (MGP), a potent inhibitor of calcification, which exerts its action by blocking BMP2. HCAECs were treated with oxidized-low density lipoprotein (ox-LDL, 80 microg/mL) or tumor necrosis factor-alpha (TNFalpha, 10 ng/mL), and the expression of Cbfa1, BMP2, and MGP was quantified by real-time PCR. Cbfa1 was expressed at low levels in untreated HCAECs, and its expression did not change with ox-LDL or TNFalpha treatment. The expression of BMP2 and MGP increased early after exposure to ox-LDL or TNFalpha (at 2-8 h), and the increase was not evident at 24 h. Ox-LDL exerted a stronger effect on MGP than on BMP2 expression. The effects of ox-LDL, but not TNFalpha, on MGP and BMP2 expression were inhibited by pretreatment of cells with an antibody directed at LOX-1, a lectin-like receptor for ox-LDL (10 microg/mL). Thus, the endothelium, when exposed to atherogenic stimuli, ox-LDL in particular, regulates the process of calcification by enhancing the expression of the bone inhibitory MGP, while the expression of Cbfa1 remains unchanged. Upregulation of BMP2 may represent a feedback upregulation in response to increase in MGP. The effect of ox-LDL appears to be mediated by LOX-1 activation.