Serum interleukin-6 and C-reactive protein are markedly elevated in acute decompensated heart failure patients with left ventricular systolic dysfunction.

Cytokines play important roles in heart failure (HF). We examined whether cytokine levels are different in acute decompensated heart failure (ADHF) patients between with left ventricular systolic dysfunction (LVSDF) and with preserved LV ejection function (PLVEF). We studied 81 HF patients who were admitted to our hospital with acute decompensation. They were divided into two groups: LVSDF (LVEF)<45% and PLVEF (LVEF45%). Serum interleukin-6 (IL-6), highly sensitive C-reactive protein (hsCRP), tumor necrosis factor alpha (TNF-alpha), and IL-18 and plasma brain natriuretic peptide (BNP) were measured on admission and at discharge. On admission, IL-6 and hsCRP were higher in LVSDF than in PLVEF. IL-6 and hsCRP decreased after treatment in LVSDF, but not in PLVEF, while plasma BNP levels decreased in both HF with treatment. There was no difference in TNF-alpha or in IL-18 level between LVSDF and PLVEF, and they did not change after treatment in either group. In conclusion, cytokine profiles were different in ADHF between those with LVSDF and PLVEF. Activation of IL-6-hsCRP pathway may play a specific role in ADHF with LVSDF.

Iron regulatory hormone hepcidin decreases in chronic heart failure patients with anemia.

BACKGROUND: The etiology of anemia is still unclear in patients with chronic heart failure (CHF). Hepcidin is an iron regulatory peptide that is synthesized in the liver to suppress iron absorption and utilization. Hepcidin synthesis is suppressed by anemia, hypoxia and erythropoiesis, and induced by inflammation. Inflammatory cytokines, such as interleukin-6 (IL-6), increase the synthesis of hepcidin, resulting in anemia of inflammation (AI). The serum hepcidin concentration in CHF patients with anemia was measured in order to better understand anemia in CHF. METHODS AND RESULTS: Serum hepcidin-25, erythropoietin (EPO), ferritin and IL-6 concentrations were measured in 61 CHF patients. Among these patients, 36 patients had anemia. A group of 16 patients without cardiac disease or anemia were recruited as controls. Serum IL-6 and EPO were higher and hepcidin-25 was lower in CHF patients with anemia than in controls. Hepcidin-25 correlated with EPO and ferritin but not with IL-6. Results of multivariable regression analysis showed that independent predictors of serum hepcidin-25 included EPO and ferritin but not IL-6. CONCLUSIONS: Serum hepcidin-25 concentrations were regulated by iron storage and erythropoiesis but not by IL-6 in CHF patients with anemia. These findings might indicate that AI is a minor cause of anemia in CHF.

Hyperglycemia induced cell growth and gene expression via the serum response element through RhoA and Rho-kinase in vascular smooth muscle cells.

The impressive correlation between cardiovascular disease and alterations in glucose metabolism has raised the likelihood that atherosclerosis, heart failure, and type 2 diabetes may share common antecedents. Postprandial hyperglycemia has been shown to play an important role on the onset and development of heart failure and cerebral infarction in several large-scale clinical trials. Recently, chronic hyperglycemia has been reported to enhance the vasoconstrictor response by Rho-kinase. We have previously reported that phenylephrine enhanced the vasoconstrictor response in a spontaneous diabetes mellitus OLETF (Otsuka-Long-Evane-Tokushima fatty) rat model. However, the mechanism of hyperglycemia in these reactions, particularly the influence of hyperglycemia on the signal transduction pathway, is still not well understood. We, therefore, examined the effect of hyperglycemia on the cell growth and gene expression of rat aortic smooth-muscle cells (RASMCs). Hyperglycemia accelerated the growth of RASMCs in a concentration-dependent manner. Furthermore, the c-fos gene expression was also increased by hyperglycemia. Phenylephrine activated the c-fos gene expression. Hyperglycemia augmented the phenylephrine-induced c-fos gene expression synergistically in a dose dependent manner. The deletion analysis revealed that the c-fos serum response element (SRE) accounts for the c-fos gene expression. RhoA, and Rho-kinase were involved in hyperglycemia-induced c-fos gene expression. An HMG-CoA reductase inhibitor, Pitavastatin, inhibited these hyperglycemia-augmented reactions by inhibiting RhoA. Hyperglycemia itself increased the cell growth and gene expression. Furthermore, it modifies and augments the cell growth and gene expression by alpha1-AR-mediated stimulation. Statin might therefore be effective for the treatment of hyperglycemia-induced cardiovascular dysfunction.

The mechanism of distinct diurnal variations of renin-angiotensin system in aorta and heart of spontaneously hypertensive rats.

Diurnal variations in plasminogen activator inhibitor-1 mRNA expression are different between the spontaneously hypertensive rats (SHRs) and the Wistar-Kyoto (WKY) rats, and between the aorta and the heart. To elucidate the mechanisms, we examined diurnal changes in the circulating renin-angiotensin system in the SHR and WKY rats. Diurnal variations in plasma renin activity (PRA), plasma angiotensin I, and aldosterone concentrations were similar between the SHR and WKY rats. On the other hand, plasma angiotensin II (Ang II) concentration in the SHR was lower than that in the WKY rats at most time points, but increased to the level of the WKY rats in the late light phase. Treatment with AT1 receptor antagonist candesartan increased plasma Ang II concentration except at ZT 8 and lessened its diurnal variation in the SHR. At the peak in plasma Ang II in the SHR, Ang II regulated genes such as transforming growth factor-beta1 and p22phox were upregulated in the aorta. On the other hand, these genes were upregulated throughout the day in the heart of SHR. Candesartan treatment increased AT1a receptor mRNA expression in the heart but not in the aorta of SHR. These findings suggest that an AT1 receptor-mediated mechanism might cause a surge in plasma Ang II concentration at the late light phase in the SHR. Homologous down-regulation of AT1a receptor by Ang II may dampen the effect of a surge in plasma Ang II concentration in the heart of SHR.

High salt intake elevated blood pressure but not changed circadian blood pressure rhythm in Otsuka Long-Evans Tokushima Fatty (OLETF) rat.

We examined the effect of high salt intake on mean arterial pressure and circadian blood pressure rhythm in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type II diabetes mellitus. Mean arterial pressure, fasting blood glucose, and fasting plasma insulin in OLETF rats were higher than those in LETO rats, their normoglycemic controls. The amplitude of circadian blood pressure rhythm in LETO rats was smaller than that in OLETF rats. High salt intake elevated blood pressure and exacerbated hyperinsulinemia, but did not change the circadian blood pressure rhythm in OLETF rats.

Mechanical stretch induced interleukin-18 (IL-18) expression through Angiotensin subtype 1 receptor (AT1R) and endothelin-1 in cardiomyocytes.

Interleukin-18 (IL-18) is a proinflammatory cytokine with multiple biological functions. We and others have demonstrated that an increased level of circulating IL-18 is one of the risk factors for cardiovascular diseases. Endothelin-1 (ET-1) has been reported to be a potent hypertrophy-promoting factor through RhoA and Rho-Kinase. Mechanical stretch induces a hypertrophic response, partly through the production of ET-1 through Endothelin A receptor (ETAR). Moreover, it has also been reported that mechanical stretch induces cardiac hypertrophy through Angiotensin subtype 1 receptor (AT1R). However, the mechanism by which the IL-18 gene expression is regulated in cardiomyocytes has not yet been fully understood. This study was designed to elucidate the functional significance of IL-18 gene expression in response to mechanical stretch. Neonatal rat cardiomyocytes cultured on silicone dishes were subjected to stretch. The moderate 20% mechanical stretch resulted in the elevation of IL-18 expression in a time-dependent manner with the maximal level achieved 36 hours after the stretch. Olmesartan, AT1R antagonist inhibited stretch-induced IL-18 expression. ETAR blockade BQ123 inhibited stretch-induced IL-18 expression. However, the Endothelin B receptor (ETBR) receptor blockade BQ788 did not inhibit this reaction. ET-1 induced IL-18 expression, with a peak induction after 4 hours of incubation. These results might suggest that stretch stimulation of cardiomyocytes induced ET-1 and, subsequently, ET-1 up-regulated the IL-18 expression. Furthermore, Fasudil, a Rho-Kinase inhibitor, and Simvastatin, a HMG-CoA reductase inhibitor, led to a significant reduction in mechanical stretch-induced IL-18 expression. These results indicated, for the first time, that IL-18 expression is induced by mechanical stretch in cardiomyocytes via the ETAR, AT1R, and the Rho/Rho-K pathways. The induction of IL-18 from cardiomyocytes by mechanical stress might cause the deterioration of cardiac functions in autocrine and paracrine fashion. The inhibition of IL-18 expression induced by mechanical stress might be one of the mechanisms that account for the beneficial cardiovascular effects of AT1R antagonist, ETAR blockade, Statin, and Rho-Kinase inhibitor.

Two giant renal aneurysms and renal arteriovenous fistula associated with cardiac insufficiency and a sustained elevation of atrial natriuretic peptide and brain natriuretic peptide.

A 64-year-old man presented with chief complaints of exertional dyspnea and palpitation. He had previously undergone left nephrolithotomies twice. A chest roentgenogram showed pleural effusion on both sides with cardiac dilation, and electrocardiography showed a frequent occurrence of ventricular premature contractions. An echocardiogram showed diffuse hypokinesis of the left ventricular wall motion (ejection fraction, 45%) and dilation of the left ventricle (left ventricular end-diastolic dimension, 61 mm). We administered diuretics, ACE inhibitors and a beta-adrenergic blocking agent after making a diagnosis of cardiac insufficiency. Because coronary angiography showed 90% stenosis of the left anterior descending coronary artery (No. 7), we performed coronary angioplasty in this locus. Though both the left ventricular wall motion and ejection fraction improved, and the clinical symptoms disappeared, the left ventricular end-diastolic dimension, and arrhythmia did not improve. Furthermore, the brain natriuretic peptide increased despite these treatments. Thereafter, a left renal artery aneurysm (extrarenal aneurysm measuring 5 cm in diameter and an intrarenal aneurysm measuring 3 cm in diameter) and a left renal arteriovenous fistula were discovered when abdominal echography was performed because of epigastric discomfort. As a result, a left total nephrectomy was performed. Subsequently, the left ventricular end-diastolic dimension and arrhythmia improved, and the brain natriuretic peptide returned to a normal value. We herein report a case that developed cardiac insufficiency due to a renal aneurysm and renal arteriovenous fistula after undergoing left nephrolithotomies twice.

Loop diuretic precipitated beriberi in a patient after pancreaticoduodenectomy: a case report.

Upper gastrointestinal tract surgery and diuretic use are 2 unrecognized causes of thiamine (vitamin B1) deficiency. Upper gastrointestinal tract surgery decreases the thiamine absorption, and diuretic use increases urinary excretion of thiamine. We present a case of a patient with a history of pancreaticoduodenectomy who had development of beriberi by diuretic use. A 68-year-old man was referred to our hospital because of pretibial pitting edema, foot numbness, and gait disturbance. He had a history of pancreaticoduodenectomy 8 years before and had been taking loop diuretics for 2 months. He had signs of polyneuropathy and hyperkinetic heart. Beriberi was suspected, and thiamine supplementation was started immediately. Edema disappeared within several days, and signs of polyneuropathy gradually subsided. Because diuretics enhance urinary thiamine excretion, practitioners should use caution for thiamine deficiency when they prescribe diuretics for patients who have a history of upper gastrointestinal surgery and potentially have latent thiamine deficiency.

Calcium phosphate coprecipitation greatly enhances transduction of cardiac myocytes and vascular smooth muscle cells by lentivirus vectors.

BACKGROUND: Lentivirus vectors provide a delivery system that can both transduce nondividing cells and integrate transgenes into the genome of target cells without cytotoxicity. However, their relatively low transduction efficiency presents a significant obstacle to progress. OBJECTIVES: In the present paper, a simple and easy method using calcium phosphate (CaPi) to enhance the efficiency of lentivirus gene transfer in both vascular smooth muscle cells and cardiac myocytes is reported. METHODS AND RESULTS: Delivery of lentivirus vectors in the presence of CaPi coprecipitates increased vector-encoded transgene expression up to 13-fold. Of interest, the magnitudes of enhancement of transgene expression by CaPi coprecipitates in 293T cells, vascular smooth muscle cells and cardiac myocytes were greater during brief periods (10 min and 120 min) of virus-cell contact than during long periods (16 h). Moreover, with a short duration of incubation with CaPi coprecipitates (up to 120 min), there was little evidence of direct cell toxicity. CaPi coprecipitates had no effect on host range specificity of ecotropic viruses and thus appears to enhance transduction efficiency physiologically by facilitating physical interaction between virus and cell. CONCLUSIONS: These data show that lentivirus with CaPi coprecipitates increases both the efficiency and the speed of gene transfer. These approaches provide an efficient method and an improved tool for research and possibly for therapy of cardiovascular diseases.

Chylomicron remnants stimulate release of interleukin-1beta by THP-1 cells.

Recent findings suggest that the oxidative modification of low-density lipoproteins (LDL) and an increase in triglyceride-rich lipoprotein particles including chylomicron remnants contribute to the progression of atherosclerosis, as does the inflammatory response. We therefore examined whether and how these lipoproteins affected interleukin (IL)-1beta release and mRNA expression for IL-1beta and IL-18 in THP-1 cells, a human monocyte cell line. Chylomicron remnants increased IL-1beta release into the conditioned medium by THP-1 in a dose- and time-dependent manner. At concentrations up to 1 microg/ml, chylomicron remnants increased IL-1beta release by 4-fold compared with the control. Neither native LDL nor oxidized LDL (OxLDL) significantly increased IL-1beta release. Chylomicron remnants increased IL-1beta mRNA expression by 3 times. Native LDL or OxLDL did not increase IL-1beta mRNA, while neither these lipoproteins nor chylomicron remnants increased IL-18 mRNA. Chylomicron remnants also increased the activities of caspase-1 and nuclear factor (NF)-kappaB significantly, while native LDL or OxLDL did not. In conclusion, chylomicron remnants stimulated IL-1beta mRNA expression and IL-1beta protein production probably via caspase-1 and NF-kappaB activation in THP-1 cells.

Transplantation of cardiotrophin-1-expressing myoblasts to the left ventricular wall alleviates the transition from compensatory hypertrophy to congestive heart failure in Dahl salt-sensitive hypertensive rats.

OBJECTIVES: We investigated whether autologous transplantation of skeletal myoblasts (MB) transferred with cardiotrophin-1 (CT-1) gene could retard the transition to heart failure (HF) in Dahl salt-sensitive (DS) hypertensive rats. BACKGROUND: Although MB is a therapeutic candidate for chronic HF, little is known about the efficiency of this strategy when applied in nonischemic HF. Cardiotrophin-1 has potent hypertrophic and survival effects on cardiac myocytes. We hypothesized that transplantation of CT-1-expressing myoblasts could provide cardioprotective effects against ventricular remodeling in DS hypertensive rats. METHODS: The DS rats were fed a high salt diet for 6 weeks and developed left ventricular (LV) hypertrophy at 11 weeks. At this stage, animals underwent MB to the myocardium with skeletal myoblasts transferred with CT-1 gene using retrovirus (transplantation of CT-1-expressing myoblasts [MB + CT], n = 31) or myoblasts alone (MB, n = 31). The sham group rats were injected with phosphate-buffered saline (n = 24). RESULTS: At 17 weeks, MB and MB + CT groups showed a significant alleviation of LV dilation and contractile dysfunction compared with the sham group. The degree of alleviation was significantly greater in the MB + CT group than the MB group (LV end-diastolic dimension: sham 7.06 +/- 0.14 mm, MB 6.51 +/- 0.16 mm, MB + CT 6.24 +/- 0.07 mm; fractional shortening: sham 32.1 +/- 1.4%, MB 38.5 +/- 1.5%, MB + CT 43.2 +/- 0.8%). Histological examination revealed that the myocyte size was 20% larger in the MB + CT group at 17 weeks than in the age-matched sham group. Upregulation of renin-angiotensin and endothelin systems during the transition to HF was attenuated by myoblast transplantation, and this effect was enhanced in the MB + CT group. CONCLUSIONS: Transplantation of skeletal myoblasts combined with CT-1-gene transfer could be a useful therapeutic strategy for HF.

Mizoribine-induced rhabdomyolysis in a rheumatoid arthritis patient receiving bezafibrate treatment.

Bezafibrate, one of fibric acid derivatives, is widely used to treat hypertriglyceridemia and diabetic dyslipidemia. Fibric acid derivatives are known to induce rhabdomyolysis as a side effect, especially when given to patients with renal dysfunction. Mizoribine, an imidazole nucleoside, is used as an immunosuppressive agent. Here, we present a case of a patient with rheumatoid arthritis who developed rhabdomyolysis while undergoing treatment with mizoribine concomitantly with bezafibrate. Drug-induced rhabdomyolysis was suspected and bezafibrate and mizoribine were discontinued, and the patient was treated with hydration. The patient's symptoms rapidly disappeared and abnormalities of blood and urine test findings also improved to normal levels within 1 week. When prescribing fibrates to patients with high risk of renal damage, caution should be exercised regarding interactions with other drugs and the potential for inducing rhabdomyolysis.

Intramuscular gene transfer of interleukin-10 cDNA reduces atherosclerosis in apolipoprotein E-knockout mice.

Atherosclerosis has a close relationship to inflammation, particularly T helper type 1 lymphocyte (Th1) response. Interleukin-10 (IL-10), is thought to suppress Th1 response. To target therapeutic strategy for atherosclerosis, we tested whether IL-10 gene transfer suppresses atherosclerosis in apolipoprotein E-knockout (apoE-KO) mice. Four-week-old apoE-KO mice were divided into two groups and either murine IL-10 cDNA plasmid or empty control vector was transferred to the femoral muscle with the use of Hemagglutinating virus of Japan (HVJ)-liposome. At 1 week after transfection, high cholesterol diet was started and continued for 8 weeks. After euthanasia, histological studies of atherosclerotic lesions and quantitative RT-PCR for Th1 cytokines (IL-12 and IFN-gamma) in spleens were performed. IL-10 cDNA gene transfer to the muscle increased plasma IL-10 levels and depressed expression of Th1 cytokines without changing plasma cholesterol levels. IL-10 gene transfer significantly reduced the atherosclerotic plaque area and the macrophage infiltrated area. IL-12 and IFN-gamma mRNA expressions in spleens and plasma IFN-gamma levels were decreased by IL-10 gene transfer. Therefore, IL-10 gene transfer changed the Th1 response and suppressed atherosclerotic lesion formation in apoE-KO mice. IL-10 could be a new target as a therapeutic tool for the treatment of atherosclerosis.

Circadian gene expression of clock genes and plasminogen activator inhibitor-1 in heart and aorta of spontaneously hypertensive and Wistar-Kyoto rats.

OBJECTIVE: Heart and aorta possess biologic clocks, but their involvement in genetic hypertension has been unknown. Plasminogen activator inhibitor-1 (PAI-1) expression is directly regulated by clock genes, while angiotensin II modulates both PAI-1 and clock gene expression. We therefore examined circadian expression of PAI-1 and clock genes, and effects of angiotensin type 1 (AT1) receptor antagonism, in heart and aorta of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. METHODS: We examined cardiac and aortic mRNA expression for PAI-1 and clock genes (Per2, Bmal1, Clock, and Dbp) every 4 h throughout the day by quantitative reverse transcription-polymerase chain reaction, and intervention with the AT1 receptor antagonist candesartan and equihypotensive hydralazine. RESULTS: Cardiac PAI-1 expression was high in the dark, while aortic PAI-1 expression was high in the light. Both cardiac and aortic PAI-1 expression were greater in SHR than in WKY rats. Candesartan treatment decreased cardiac PAI-1 expression only in the dark in WKY rats but throughout the day in SHR. Candesartan but not hydralazine strongly attenuated circadian fluctuation of aortic PAI-1 mRNA in SHR and WKY rats. Clock genes oscillated synchronously in heart and aorta of SHR and WKY rats. Clock gene expression was increased in heart but not aorta of SHR. Candesartan did not affect clock gene expression. CONCLUSIONS: Enhanced expression of clock genes may increase PAI-1 expression in concert with activated renin-angiotensin system in SHR heart. Rather than clock genes, the renin-angiotensin system induces daily fluctuation and increased expression of aortic PAI-1 mRNA in SHR.

The renin-angiotensin system is involved in the production of plasminogen activator inhibitor type 1 by cultured endothelial cells in response to chylomicron remnants.

Triglyceride-rich lipoproteins have been suggested to promote atherosclerosis. Plasminogen activator inhibitor type 1 (PAI-1) plays an important role in the events of cardiovascular pathophysiology. The renin-angiotensin system influences various vascular functions, including PAI-1 production. We examined whether or not chylomicron remnants increased PAI-1 mRNA and protein production in endothelial cells and whether or not an inhibition of the renin-angiotensin system interfered with this effect. Chylomicron remnants were isolated from functionally hepatectomized rats injected with chylomicrons. Human umbilical vein endothelial cell cultures (HUVECs) were incubated with chylomicron remnants with or without an angiotensin-converting enzyme inhibitor (temocaprilat), an angiotensin II receptor type 1 antagonist (RNH-6270), or an angiotensin II receptor type 2 antagonist (PD123319). Chylomicron remnants increased PAI-1 secretion in HUVECs (0.5 microg/ml; 128.3 +/- 6.1%, the mean +/- SEM) as well as angiotensin II (10 nmol/l; 130.7 +/- 9.5%) in 18 h, as compared with the controls, as well as stimulated PAI-1 mRNA expression to a maximum level at 4 h. Temocaprilat and RNH-6270, but not PD123319, attenuated all of these effects. Chylomicron remnants enhanced nuclear extract binding to a very low-density lipoprotein response element in the PAI-1 promoter region and activated nuclear factor-kappaB. Extracellular signal-regulated kinase (ERK 1/2) was phosphorylated in response to chylomicron remnants. These effects were inhibited by temocaprilat or RNH-6270. In conclusion, chylomicron remnants increased protein secretion and mRNA expression of PAI-1 in HUVECs. Inhibition of the renin-angiotensin system reduced this stimulation.

Cardiac myocytes are recruited by bone marrow-derived cells in intact murine heart.

It is generally believed that the cardiac myocytes withdraw from the cell cycle shortly after birth and thereafter any loss of myocardial tissue cannot be repaired. However, recent reports indicate that cardiac myocytes can be regenerated by stem cells derived from bone marrow in the damaged hearts. In this study, we investigated whether bone marrow-derived cells can differentiate into cardiac myocytes in the intact hearts. We performed bone marrow transplantation from syngenic male mice to female c57/B6 mice. In female mice's hearts, the presence of cells from male mice was examined by FISH method that detects Y chromosome. Using the same samples, we also performed immunohistochemical staining with muscle specific antibodies. In the heart sections of female mice, there were some cells that were considered as differentiated myocytes derived from male bone marrow (0.01~0.09% of total myocytes) and the proportion of the cells increased as the period after bone marrow transplantation became longer (3 months after vs. 8 months after). These results suggest that, not only in the damaged heart but also in the intact heart, a portion of cardiac myocytes is recruited by bone marrow-derived cells.

Decrease in serum adiponectin levels in response to treatment predicts good prognosis in acute decompensated heart failure.

Adiponectin is a cardioprotective adipocytokine. Serum adiponectin concentration decreases in patients who are obese but increases in patients with chronic heart failure (CHF). The aim of this study was to explore the temporal changes in serum adiponectin concentration following treatment for acute decompensated heart failure (ADHF). Serum adiponectin was measured on admission and at discharge in 95 patients who were admitted to our hospital with ADHF. Ten patients without heart failure (HF) served as controls. Serum adiponectin concentration was higher on admission in HF patients than in the controls (22.6±13.3 µg/mL vs 9.3±3.9 µg/mL, P<.01). Serum adiponectin concentration decreased after treatment in HF patients (18.0±11.7 µg/mL vs 22.6±13.3 µg/mL, P<.01). The larger temporal decrease in adiponectin level in ADHF was associated with the lower incidence of cardiac death or HF hospitalizations (log-rank, P<.05). Serum adiponectin concentration was elevated in ADHF and decreased following the treatment. How much serum adiponectin decreases in response to treatment in ADHF is an important determinant of the prognosis.

OCT assessment of thin-cap fibroatheroma distribution in native coronary arteries.

OBJECTIVES: We evaluated the geographic distribution of thin-cap fibroatheromas (TCFAs) in the coronary arteries using optical coherence tomography (OCT), a high-resolution imaging modality. BACKGROUND: Plaque rupture is the most frequent cause of acute myocardial infarction (AMI). It has been recognized that TCFA is the primary plaque type at the site of plaque rupture. METHODS: We performed 3-vessel OCT examinations in 55 patients: 35 AMI and 20 stable angina pectoris patients. The criteria for TCFA in an OCT image was a lipid-rich plaque with fibrotic cap thickness <65 microm. The distance between each TCFA location and the respective coronary artery ostium was measured with motorized OCT imaging pullback. The total length of all 3 coronary arteries imaged by OCT pullbacks was 82 +/- 21 mm in the left anterior descending coronary artery (LAD), 67 +/- 26 mm in the left circumflex coronary artery (LCx), and 104 +/- 32 mm in the right coronary artery (RCA). RESULTS: OCT detected 94 TCFAs in 165 coronary arteries. The minimum fibrous-cap thickness of TCFAs was 57.4 +/- 5.4 microm in AMI patients, and 55.9 +/- 7.3 microm in stable angina pectoris patients (p = 0.4). Of the total of 94 TCFAs, 28 were detected in the LAD, 18 in the LCx, and 48 in the RCA. Most LAD TCFAs were located between 0 and 30 mm from the LAD ostium (76%). Conversely, LCx and RCA TCFAs were evenly distributed throughout the entire coronary length. The clustering of the TCFAs was similar in culprit segments as compared with nonculprit segments. In AMI patients, most LAD TCFAs were distributed near side branches, mainly positioned opposite the side branch bifurcation. CONCLUSIONS: Three-vessel OCT imaging showed that TCFAs tend to cluster in predictable spots within the proximal segment of the LAD, but develop relatively evenly in the LCx and RCA arteries.