Relationship between left main coronary artery plaque burden and nonleft main coronary atherosclerosis: results from the PROSPECT study.

Objectives: Whether the severity of left main coronary artery (LMCA) disease reflects LMCA and overall coronary atherosclerotic burden is not known. We aimed to assess nonculprit LMCA disease characteristics and the relationship with atherosclerosis in the rest of the coronary arteries as well as patient outcomes.

Patients And Methods: In the PROSPECT study, 697 patients with acute coronary syndromes underwent three-vessel gray-scale and radiofrequency intravascular ultrasound after percutaneous coronary intervention.

Relationship Between Platelet Reactivity and Culprit Lesion Morphology: An Assessment From the ADAPT-DES Intravascular Ultrasound Substudy.

Objectives: This study evaluated the relationship between platelet reactivity and plaque morphology using grayscale and radiofrequency intravascular ultrasound (IVUS) virtual histology (VH).

Background: Recent studies have reported that high on-treatment platelet reactivity (HPR) is associated with higher plaque volume and the presence of multivessel disease; however, the association between HPR and plaque morphology has not been evaluated.

Methods: The ADAPT-DES (Dual AntiPlatelet Therapy With Drug Eluting Stents) intravascular ultrasound substudy was a prospective, multicenter, observational study of 8,582 patients undergoing percutaneous coronary intervention with drug-eluting stents in whom platelet reactivity on clopidogrel was assessed routinely.

Multi-laboratory inter-institute reproducibility study of IVOCT and IVUS assessments using published consensus document definitions.

Aims: The aim of this study was to investigate the reproducibility of intravascular optical coherence tomography (IVOCT) assessments, including a comparison to intravascular ultrasound (IVUS). Intra-observer and inter-observer variabilities of IVOCT have been previously described, whereas inter-institute reliability in multiple laboratories has never been systematically studied.

Methods And Results: In 2 independent laboratories with intravascular imaging expertise, 100 randomized matched data sets of IVOCT and IVUS images were analysed by 4 independent observers according to published consensus document definitions.

Age-related effects of smoking on culprit lesion plaque vulnerability as assessed by grayscale and virtual histology-intravascular ultrasound.

Background: Although smoking is a risk factor for coronary atherosclerosis, the age-related impact on lesion characteristics and plaque instability remains unclear.

Patients And Methods: In ADAPT-DES, 780 patients with 916 culprit lesions were evaluated by preprocedural grayscale and virtual histology-intravascular ultrasound.

Results: Current smokers (smoking within 1 month) more often presented with acute coronary syndrome (67 vs.

Effect of obesity on coronary atherosclerosis and outcomes of percutaneous coronary intervention: grayscale and virtual histology intravascular ultrasound substudy of assessment of dual antiplatelet therapy with drug-eluting stents.

Background: Obesity is a cardiovascular risk factor, but the obesity paradox in patients undergoing percutaneous coronary intervention is poorly understood.

Methods And Results: Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents (ADAPT-DES) was a prospective, multicenter study of patients undergoing drug-eluting stent implantation. Overall, 780 patients (916 culprit lesions) were evaluated by grayscale and virtual histology-intravascular ultrasound pre-percutaneous coronary intervention.

Mechanical complications of everolimus-eluting stents associated with adverse events: an intravascular ultrasound study.

Aims: Mechanical complications contribute to bare metal and first-generation drug-eluting stent (DES) failure. However, the importance of the mechanical complications of second-generation DES remains unclear. We report mechanical complications associated with everolimus-eluting stent (EES) failures.

Compensatory enlargement of the left main coronary artery: insights from the PROSPECT study.

Objectives: Glagov proposed that remodeling delayed development of significant coronary artery stenoses until plaque occupied, on average, 40% of arterial area (40% plaque burden). The aim of the current study was to confirm the previously proposed concept of coronary remodeling as first described by Glagov who studied postmortem left main coronary arteries (LMCAs).

Methods: Using the in-vivo intravascular ultrasound data from the Providing Regional Observations to Study Predictors of Events in the Coronary Tree (PROSPECT) study, we evaluated 552 LMCAs in 552 patients.

Bypass to the left coronary artery system may accelerate left main coronary artery negative remodeling and calcification.

Aims: This study aimed to use intravascular ultrasound (IVUS) data to reveal the mechanism of lesion progression in the native coronary circulation proximal to bypass grafts after coronary artery bypass grafting (CABG).

Methods And Results: We reviewed IVUS images in 86 patients with an angiographically significant left main coronary artery (LMCA) stenosis. Overall, 41 patients underwent CABG more than 6 months (mean 8.

Azelnidipine inhibits Msx2-dependent osteogenic differentiation and matrix mineralization of vascular smooth muscle cells.

Vascular calcification is an active and regulated process that is similar to bone formation. While calcium channel blockers (CCBs) have been shown to improve outcomes in atherosclerotic vascular disease, it remains unknown whether CCBs have an effect on the process of vascular calcification. Here we investigated whether CCBs inhibit osteogenic differentiation and matrix mineralization of vascular smooth muscle cells induced by Msx2, a key factor of vascular calcification.

Runx2/Smad3 complex negatively regulates TGF-β-induced connective tissue growth factor gene expression in vascular smooth muscle cells.

Aim: Connective tissue growth factor (CTGF), a direct target gene of transforming growth factor-β (TGF-β) signaling, plays an important role in the development of atherosclerosis. We previously showed that Runx2, a key transcription factor in osteoblast differentiation, regulates osteogenic conversion and dedifferentiation of vascular smooth muscle cells (VSMCs). In this study, we investigated the hypothesis that Runx2 modulates CTGF gene expression via the regulation of TGF-β signaling.

Notch induces myofibroblast differentiation of alveolar epithelial cells via transforming growth factor-{beta}-Smad3 pathway.

Notch is an ancient cell-signaling system that regulates the specification of cell fate. This study examined the role of Notch in the epithelial-mesenchymal transition (EMT) and myofibroblast differentiation of cultured RLE-6TN cells (i.e.

Activation of receptor for advanced glycation end products induces osteogenic differentiation of vascular smooth muscle cells.

Aim: Vascular calcification is prevalent in patients with diabetes and chronic kidney disease. Receptor for advanced glycation end products (RAGE) and its multiple ligands have been implicated in the pathogenesis of accelerated atherosclerosis; however, little is known about the effects of RAGE activation on vascular calcification.

Methods And Results: Cultured rat and human aortic smooth muscle cells (HASMC) were transduced with adenovirus expressing RAGE.

Notch signaling pathway enhances bone morphogenetic protein 2 (BMP2) responsiveness of Msx2 gene to induce osteogenic differentiation and mineralization of vascular smooth muscle cells.

Vascular calcification is regulated in a process similar to bone formation. BMP2 (bone morphogenetic protein 2) is essential for osteoblastic differentiation of mesenchymal progenitor cells and thus has been implicated in the development of vascular calcification. Here we examined whether Notch signaling interacts with BMP2 signaling to regulate osteogenic differentiation and mineralization of vascular smooth muscle cells (SMCs).

Association between fibroblast growth factor 23 and left ventricular hypertrophy in maintenance hemodialysis patients. Comparison with B-type natriuretic peptide and cardiac troponin T.

Background: Fibroblast growth factor 23 (FGF-23) is a novel bone-derived phosphate-regulating hormone, and serum FGF-23 levels are associated with mortality among hemodialysis (HD) patients. However, the pathophysiological role of FGF-23 in those patients remains unclear, so the association between serum FGF-23 levels and known cardiac biomarkers or echocardiographic measurements were investigated in long-term HD patients without cardiac symptoms.

Methods And Results: The 87 consecutive patients treated in a single HD center (51 males, 36 females; mean age 64 years, mean HD duration 5.

Fibroblast growth factor-2 induces osteogenic differentiation through a Runx2 activation in vascular smooth muscle cells.

Expression of bone-associated proteins and osteoblastic transcription factor Runx2 in arterial cells has been implicated in the development of vascular calcification. However, the signaling upstream of the Runx2-mediated activation of osteoblastic program in vascular smooth muscle cells (VSMC) is poorly understood. We examined the effects of fibroblast growth factor-2 (FGF-2), an important regulator of bone formation, on osteoblastic differentiation of VSMC.

Notch signaling induces osteogenic differentiation and mineralization of vascular smooth muscle cells: role of Msx2 gene induction via Notch-RBP-Jk signaling.

Objective: Vascular calcification is closely correlated with cardiovascular morbidity and mortality. Here, we demonstrate the role of Notch signaling in osteogenic differentiation and mineralization of vascular smooth muscle cells (SMCs).

Methods And Results: The Msx2 gene, a key regulator of osteogenesis, was highly induced by coculture with Notch ligand-expressing cells or overexpression of Notch intracellular domains (NICDs) in human aortic SMCs (HASMCs).

PIAS1 mediates TGFbeta-induced SM alpha-actin gene expression through inhibition of KLF4 function-expression by protein sumoylation.

Objective: TGFbeta and proliferation/phenotypic switching of smooth muscle cells (SMCs) play a pivotal role in pathogenesis of atherosclerotic and restenotic lesions after angioplasty. We have previously shown that the protein inhibitor of activated STAT (PIAS)1 activates expression of SMC differentiation marker genes including smooth muscle (SM) alpha-actin by interacting with serum response factor (SRF) and class I bHLH proteins. Here, we tested the hypothesis that TGFbeta activates SM alpha-actin through PIAS1.

Runx2 represses myocardin-mediated differentiation and facilitates osteogenic conversion of vascular smooth muscle cells.

Phenotypic plasticity and the switching of vascular smooth muscle cells (SMCs) play a critical role in atherosclerosis. Although Runx2, a key osteogenic transcription factor, is expressed in atherosclerotic plaques, the molecular mechanisms by which Runx2 regulates SMC differentiation remain unclear. Here we demonstrated that Runx2 repressed SMC differentiation induced by myocardin, which acts as a coactivator for serum response factor (SRF).