Biomedical subjects

Gad Keren

Publications and source records attributed to Gad Keren.

At least 19 recordsLinked to original sources

PubMed2006

Circulating endothelial progenitor cells in patients with cardiac syndrome X.

BACKGROUND: Cardiac syndrome X (CSX) encompasses the constellation of anginal chest pain in the presence of a pathological functional test and a normal coronary angiogram. Endothelial progenitor cells (EPCs) in the peripheral circulation contribute to tissue vascularisation. OBJECTIVE: To investigate the number and functional properties of circulating EPCs in patients with CSX. METHODS: 17 patients with CSX and a referent population (n = 20) were matched for age, atherosclerotic risk factors and use of drugs. Numbers of EPCs were studied by FACS, and their functional properties, including their proliferative capacity, adherence to matrix and mature endothelial cells as well as their ability to support in vitro tube formation, were investigated. Levels of soluble markers that associate with peripheral mobilisation and homing were studied in the serum samples of all subjects. RESULTS: Patients with CSX had significantly increased numbers of circulating EPCs as compared with the referent population (both CD34+/KDR and CD34+/CD133+). The proliferative capacity of EPCs and their ability to support in vitro tube formation were significantly impaired in patients with CSX as compared with the referent population. However, adhesiveness of EPCs from patients with CSX to fibronectin and cultured mature endothelial cells was enhanced as compared with the referent population. Serum vascular endothelial growth factor correlated with peripheral CD34+/KDR cell numbers, whereas serum concentration of erythropoietin correlated with the number of circulating CD34+/CD133+ cells CONCLUSION: Patients with CSX have a significantly altered circulating EPC phenotype that could potentially aid in understanding the complex pathogenesis of the syndrome.

Adiponectin↗

PubMed2006

Cardiac dysfunction in patients with systemic lupus erythematosus and antiphospholipid syndrome.

OBJECTIVE: To comparatively assess the parameters of systolic and diastolic cardiac function in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). METHODS: Consecutive patients (n=74) who were free of cardiovascular symptoms were divided into four groups: (1) SLE (n=23); (2) SLE with antiphospholipid antibodies (aPL; n=18); (3) SLE with APS (n=20); and (4) primary antiphospholipid syndrome (PAPS; n=13). Pulsed, continuous, colour Doppler echocardiography, and M-mode and B-mode studies were performed. RESULTS: Left ventricular end diastolic and end systolic dimensions were higher in SLE as compared with patients with PAPS (p=0.022 and 0.022, respectively), with a trend towards a lower fractional shortening in SLE (p=0.07), suggesting systolic dysfunction. Parameters of diastolic function were more impaired in patients with APS, reflected by lower left ventricular and right ventricular E wave to A wave (E:A) ratios in patients with APS (groups 3, 4) compared with those without APS (groups 1, 2; 1.15 (0.40) v 1.49 (0.43), p=0.001 and 1.19 (0.31) v 1.49 (0.41), p=0.001, respectively) and a more prolonged left ventricular isovolumic relaxation time (IVRT; 94.2 (24.6) v 84.4 (17) ms, respectively, p=0.055). Patients with APS were older than those without APS (47.12 (14.86) v 34.29 (12.6), p=0.0001). Patients with SLE were younger than those with PAPS (38.19 (14.68) v 48.53 (13.97), p=0.023). CONCLUSION: Abnormal echocardiographic findings were detected frequently in asymptomatic patients with SLE or PAPS. Although patients with SLE were younger, left ventricular systolic function was more impaired in patients with SLE compared with those with PAPS, whereas left ventricular and right ventricular diastolic function, as reflected by IVRT and E:A ratios, were significantly more impaired in patients with APS.

Adult↗

PubMed2006

Altered status of CD4(+)CD25(+) regulatory T cells in patients with acute coronary syndromes.

AIMS: Considerable evidence supports the role of innate and adaptive immunity in the progression and destabilization of the atheromatous plaque. Naturally occurring CD4(+)CD25(+) regulatory T cells (Tregs) are a subpopulation of lymphocytes that are capable of suppressing the progression of experimental autoimmune disorders. We have hypothesized that peripheral numbers and function of Tregs would be deranged in patients with acute coronary syndromes (ACS). METHODS AND RESULTS: Peripheral numbers of Tregs were evaluated by FACS employing labelled antibodies to CD4 and CD25. Functional suppressive properties of Tregs were assayed by establishing a triple-cell culture in which purified Tregs were incubated with irradiated antigen-presenting cells and anti-CD3-activated responder T cells. Proliferation in the presence or absence of oxidized LDL (oxLDL) was evaluated by thymidine incorporation. mRNA and protein content of foxp3, a master transcriptional regulator of Tregs, were determined for all subjects. Patients with ACS exhibited significantly reduced numbers of peripheral Tregs as compared with patients with stable angina and normal coronary artery subjects. Moreover, oxLDL induced a more profound reduction in Treg numbers in patients with ACS. Tregs in ACS patients were significantly compromised as their ability to suppress responder CD4(+)CD25(-) T-cell proliferation was attenuated. mRNA and protein content of foxp3 were significantly reduced in purified Tregs obtained from patients with ACS. CONCLUSION: In patients with ACS, naturally occurring CD4(+)CD25(+) Treg numbers are reduced and their functional properties compromised. These findings may aid in understanding the mechanisms leading to culprit plaque associated T-cell activation in patients with ACS.

Acute Disease↗

PubMed2006

Autoantibodies to cardiac troponin I in patients with idiopathic dilated and ischemic cardiomyopathy.

BACKGROUND: Progressive dilatation and functional compromise of heart function is attributed to a variety of pathogenic mechanisms. Experimental data suggests that autoantibodies could promote myocardial damage by inducing either inflammation or alternatively, augmentation of Ca2+ currents or activation of surface receptors on cardiomyocytes. Cardiac troponin I (cTpnI) is an essential protein component of the contractile heart. Herein, we studied the presence and functional properties of autoantibodies to cTpnI in patients with idiopathic dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM). METHODS AND RESULTS: Anti-cTpnI antibody ELISA was established for assessment of sera obtained from 33 patients with ICM, 32 with DCM and 42 healthy subjects. Binding specificity of purified cTpnI-reactive IgG fractions from patients with ICM and DCM was confirmed by competitive inhibition studies employing fluid-phase cTpnI. The effect of IgG preparations on intracellular Ca2+ ([Ca2+]i) transients was tested in cultured neonatal rat ventricular myocytes (NRVM). Six of the 33 ICM patients (18.2%) and 5 of the 32 DCM patients (15.6%) had positive anti-cTpnI antibody titer as compared to none in the healthy subjects. Purified IgG from positive patients appeared specific to cTpnI. IgG preparations reactive with cTpnI did not exhibit measurable effects on [Ca2+]i transients in cultured NRVM nor did they bind the respective cells by direct immunofluorescence. CONCLUSION: IgG antibodies to TpnI are increased in a significant number of patients with both ICM and idiopathic DCM, yet it appears that these autoantibodies cannot bind heart muscle cells or influence [Ca2+]i transients.

Adult↗

PubMed2006

Erythropoietin improves myocardial performance in doxorubicin-induced cardiomyopathy.

AIMS: Doxorubicin (Dox) is a potent chemotherapeutic agent associated with severe cardiotoxicity. Erythropoietin (Epo) has recently been shown to exhibit proangiogenic properties related to endothelial progenitor cell (EPC) mobilization. We tested the hypothesis that EPC are compromised in rats with Dox-induced cardiotoxicity and correction of this functional impairment by treatment with Epo could result in attenuation of myocardial dysfunction. METHODS AND RESULTS: Wistar rats were either treated with two different doses of Epo (20U or 200U) or PBS (n = 40 in each group) for four consecutive weeks, followed by Dox administration. In a second study, EPC obtained from healthy rats were transfused intravenously (n = 20/group) prior to induction of Dox cardiomyopathy. EPC from healthy subjects were evaluated for their proliferative and migratory properties in the presence or absence of Dox and Epo pre-treatment. Echocardiography demonstrated an improvement in fractional shortening (FS) in Epo-treated rats. Epo treatment was associated with a reduced mortality in both Epo-treated groups. Circulating EPC numbers were three times higher in Epo-treated compared with non-treated animals. Adhesive properties, migration, and tube formation capacity in matrigel of EPCs from both Epo-treated groups as compared with controls were significantly enhanced. EPC transfer to Dox-treated rats led to functional myocardial improvement equivalent to the protection afforded by treatment with Epo. In EPC obtained from humans, pre-incubation with Epo significantly attenuated the anti-proliferative and anti-migratory effects of treatment with Dox. CONCLUSION: Epo treatment is potentially protective against myocardial dysfunction induced by Dox. These effects are partially mediated by enhancement in the number of EPC and their functional properties.

Animals↗

PubMed2006

Effects of losartan + L-arginine on nitric oxide production, endothelial cell function, and hemodynamic variables in patients with heart failure secondary to coronary heart disease.

The purpose of the present study was to evaluate the effects of losartan and the combination of losartan and L-arginine on endothelial function and hemodynamic variables in patients with heart failure (HF). Endothelium-dependent vasodilation is impaired in patients with HF. It was hypothesized that the administration of losartan and the combination of losartan and L-arginine might increase nitric oxide production and have a beneficial additive effect on endothelial function and hemodynamic variables in patients with HF. Nine patients with HF (ejection fraction<35%) were given losartan 50 mg orally on 2 consecutive days. On the second day, 1 hour after losartan 50 mg administration, L-arginine 20 g was given by intravenous infusion. Endothelial function in the form of endothelium-dependent brachial artery flow-mediated vasodilation (FMV) was measured by ultrasound. Hemodynamic variables were estimated using Doppler echocardiography at baseline and at 2 and 4 hours after losartan alone and after combination therapy. Urinary levels of nitrite (NO2) or nitrate (NO3) were measured. Four hours after losartan administration, significant reductions in systemic vascular resistance and estimated end-systolic elastase were observed. On the second day, 1 hour after L-arginine infusion, an additive hemodynamic effect was observed, with significant increases in the cardiac index and stroke volume and significant reductions in systemic vascular resistance and calculated left ventricular end-diastolic pressure. A trend toward improved FMV was observed with losartan alone, but without statistical significance. Combination therapy significantly improved postintervention FMV compared with baseline. The increase in urinary nitric oxide excretion after losartan treatment and combination therapy was significantly correlated with improved hemodynamic variables and improved FMV. In conclusion, losartan induces significant afterload reduction, reduced contractility, and increased nitric oxide urinary excretion. The combination of L-arginine and losartan seems to have superior effects on hemodynamic variables and endothelium-dependent vasodilation compared with losartan alone.

Administration, Oral↗

PubMed2006

Long-term effects of dual-chamber pacing with periodic echocardiographic evaluation of optimal atrioventricular delay in patients with hypertrophic cardiomyopathy >50 years of age.

Various treatment modalities have been introduced to reduce the subaortic pressure gradient in patients with obstructive hypertrophic cardiomyopathy, including pacemaker insertion. Complete ventricular capture during pacing is essential and requires optimization of the atrioventricular interval (AVI). In this study, a protocol using echocardiographic examination assessing the changes in the left ventricular outflow tract (LVOT) gradient in different AVIs, pacing rates, and pacing modes was used for optimal pacemaker programming. Twenty-five patients with obstructive hypertrophic cardiomyopathy were implanted with DDD pacemakers and evaluated prospectively. The LVOT gradient was measured during periodic evaluations every 3 to 6 months. Gradient measurements were done with 5 different AVIs and 3 different rate combinations. After each evaluation, the optimal AVI, pacing rate, and mode were set on the basis of the minimal LVOT gradient not associated with systolic arterial cuff pressure reduction. Follow-up ranged from 18 to 126 months. Peak LVOT gradient immediately decreased in 92% of patients. During follow-up, the optimal AVI was prolonged in most patients. Sixty-four percent of patients showed a clear relation between pacemaker modifications and gradient reduction. In 75% of these patients, optimal gradient reduction required repeated AVI and pacing rate programming on the basis of echocardiographic evaluation. Symptoms decreased in 92% of patients, and New York Heart Association class improved significantly (3.1+/-0.7 vs 1.3+/-0.4, p<0.001) during follow-up. The symptomatic reduction was positively correlated with the LVOT gradient reduction. In conclusion, DDD pacing is effective in reducing the LVOT gradient and improving functional capacity in adult patients with hypertrophic cardiomyopathy. Pacemaker programming with the periodic echocardiographic evaluation of the optimal AVI, pacing rate, and mode is imperative for optimal results.

Aged↗

PubMed2006

Cellular autoimmunity to cardiac myosin in patients with a recent myocardial infarction.

After a large myocardial infarction (MI) a progressive remodeling process can occur that results in a severe mechanical dysfunction of the heart. Among the determinants of remodeling, immune mediated inflammation has been suggested as an important contributor. However, the role of autoimmunity to cardiac antigens that are released to the circulation has not been sufficiently addressed. Cardiac myosin is a contractile protein that is unique to the myocardium and has been shown to induce a humoral immune response in patients after MI, and to trigger an autoimmune myocarditis in experimental rats and mice. In the current study, we evaluated humoral and cellular immune responses to myosin in patients with and without a history of recent MI. Eighteen patients with MI, 2 weeks to 4 months prior to initiation of the study, and eighteen control subjects were enrolled. Peripheral blood mononuclear cells (PMBC) were obtained and subjected to priming with different concentrations of cardiac myosin. Interferon-gamma and TNF-alpha were measured in conditioned medium obtained from the cultured PMBC upon priming with cardiac myosin. Humoral immune responses were also assessed by evaluating IgG anti-myosin antibodies. We have found that a third of the patients with the recent history of MI and none of the control subjects had a proliferative response to cardiac myosin evident by stimulation indices greater than 1.5. No differences were detected between the patients and controls with regard to IFN-gamma and TNF-alpha secreted by their PMBC, nor were there differences in the serum levels of IgG anti-myosin antibodies. Thus, in patients with a recent history of MI, cellular autoimmunity to cardiac myosin is present as compared with controls. It remains to be determined whether this autoimmune response is associated with an adverse outcome.

Autoimmunity↗

PubMed2006

Serum levels of anti heat shock protein 70 antibodies in patients with stable and unstable angina pectoris.

BACKGROUND: The heat shock protein (HSP) family comprises approximately 24 proteins displaying a high degree of sequence homology between different species. The induction of self-HSP immune reactivity is thought to be involved in the pathogenesis of several diseases. Antibodies to HSP60/65 have been demonstrated in the sera of patients with coronary artery disease. Moreover, the target antigens of the antibodies HSP60 and HSP70 are both expressed in smooth muscle cells and macrophages within atherosclerotic lesions. In this retrospective, case control study, we investigated whether patients with established atherosclerosis, with either stable or unstable angina have high levels of antibodies to HSP70. METHODS AND RESULTS: Patients with stable angina (n = 40) were from the outpatient clinic whereas patients with unstable angina (n = 91) were recruited upon admission and prior to performance of coronary angiography. Control patients (n = 18) were healthy subjects with no evidence of coronary artery disease. Serum levels of anti-HSP70 antibodies were assayed by ELISA. Patients with stable and unstable angina exhibited lower serum levels of antibodies to HSP70 (0.202+/-0.113 and 0.201+/-0.115, respectively) in comparison to control subjects (0.364+/-0.199, P = 0.0001 for both comparisons). Serum levels of antibodies to HSP70 did not differ significantly between patients with stable and unstable angina. No differences in serum levels of antibodies to HSP70 were evident between baseline and follow up in the patients with unstable angina. CONCLUSIONS: Patients with coronary atherosclerosis possess lower levels of anti-HSP70 antibody levels. Further research is required to explore whether higher levels of anti-HSP70 antibodies have a predictive value in coronary atherosclerosis.

Aged↗

PubMed2006

Coronary ostium-straight tube or funnel-shaped? A computerized tomographic coronary angiography study.

BACKGROUND: The 3D configuration of the aortic-coronary junction is decisive in stenting ostial coronary lesions. We hypothesized that it varies between straight to funnel-shaped tubes and studied arterial orifices using computerized tomographic coronary angiography (CTCA). METHODS AND RESULTS: Axial and sagittal 2-D and volumetric 3-D reconstructions of the aorto-coronary junction were performed in 25 patients who underwent CTCA. The following measurements of the left main (LM) and right coronary (RCA) arteries ostia were obtained: the coronary orifice broad base diameter, the diameter of the coronary vessel most proximal segment, the distance between them, and the angles of the aortic-coronary junction. All patients exhibited a funnel-shaped aortic-coronary junction in at least one plane, and none had an entirely straight tube shape. The RCA take-off had symmetric angling in both the axial and sagittal planes in only one patient, while the LM did not have a symmetric origin in either plane in any patient. The mean coronary orificial funnel depth and ostial cross-sectional diameters were measured. CONCLUSION: The frequency of funnel-shaped and asymmetry of the aortic-coronary junction configuration needs to be considered in designing stents for aortic-ostial coronary lesions in order to achieve optimal results and reduce restenosis.

Adult↗

PubMed2006

Comparative analysis of methods for assessment of circulating endothelial progenitor cells.

The number and properties of endothelial progenitor cells (EPC) in disease states is of considerable interest due to the importance attributed to this distinct cell population. However, there has been no study comparing each of the methods employed in the same sampled individuals. Herein, we performed an analysis of several methods used for circulating EPC assessment and correlated them with humoral factors known to influence their numbers. Thirty-eight individuals (mean age of 34 +/- 9 years) were tested. Peripheral blood mononuclear cells were obtained and stained for FACS analysis with antibodies to CD34, CD45, CD133, and KDR and the remaining cells grown under endothelial cell conditions for assessment of colony-forming unit (CFU) numbers and adhesive properties. Levels of circulating vascular endothelial growth factor (VEGF), erythropoietin (EPO), and C-reactive protein (CRP) were determined and correlated with each of the EPC markers. CFU numbers did not correlate with CD34/KDR or CD34/CD133/KDR and negatively correlated with CD34/ CD133 numbers. CD34/KDR numbers correlated with CD34/CD133/KDR, but not with CD34/ CD133. Only CD34/KDR and CD34/CD133/KDR correlated with VEGF serum levels. The number of EPC adhering to fibronectin and endothelial cells correlated with CFU numbers and not with either of the EPC membrane markers. Current methods for quantitatively assessing numbers of circulating EPC are not correlated. VEGF serum levels are associated only with CD34/KDR and CD34/ CD133/KDR, whereas CFU numbers correlate with EPC functional properties. These findings may suggest that CD34/KDR is more appropriate for the definition of circulating EPC, whereas CFU numbers are more likely to reflect their ability to proliferate.

Adult↗

PubMed2006

The role of erythropoietin in myocardial protection: potential mechanisms and applications.

The glycoprotein erythropoietin was originally discovered as a principal regulator that promotes the survival, proliferation and differentiation of erythroid progenitor cells. Despite potentially detrimental effects, such as increased blood pressure and hyperviscosity, recombinant human erythropoietin has been demonstrated to be a safe drug, as millions of anemia sufferers have received it over the last decade as a form of treatment. Recently, erythropoietin receptors have been discovered in a variety of tissues, including the cardiovascular system, and erythropoietin has been demonstrated to have a beneficial effect in congestive heart failure patients with anemia. The purpose of this review is to summarize the pleiotropic cardioprotective effects of erythropoietin in the cardiovascular system and to evaluate its potential role as a biomarker in these disorders.

Animals↗

PubMed2006

[Surgical ventricular restoration--new horizons in the treatment of ischemic cardiomyopathy].

Heart failure is a major health problem with increasing prevalence due to aging of the population and in addition to an increase in effective treatment and early myocardial reperfusion during acute myocardial infarction. Postinfarction left ventricular remodeling is characterized by chamber dilatation with an abnormal spherical shape leading to systolic and diastolic dysfunction frequently associated with mitral valve insufficiency and eventually heart failure. Intensive medical management reduces symptoms and improves survival. However, patients who are in NYHA functional class III or IV still have a poor prognosis. In this review article we will endeavor to summarize the emerging surgical approach "surgical ventricular restoration" for treating ventricular remodeling and ischemic cardiomyopathy. These concepts of restoration of the elliptical shape of the left ventricle and re-establishing the normal structure of the sub-valvular mitral apparatus are performed recently in our department.

Cardiac Surgical Procedures↗

PubMed2006

[Endothelial progenitor cells (EPCs)--new tools for diagnosis and therapy].

Accumulating evidence suggests that postnatal bone marrow is a source of cells that can participate in postnatal neovascularization and vascular homeostasis. Among these cells, a scarce population of endothelial progenitor cells (EPCs) have the capacity to migrate to the peripheral circulation, proliferate and differentiate into mature endothelial cells in response to stimulating signals emanating from vascular injuries or during tumor growth. Questions persist, however, regarding the precise panel of cell surface markers that defined EPCs, as well as the different mechanisms stimulating or inhibiting their mobilization and differentiation. In the last decade, EPCs number and function have been correlated with risk factors for cardiovascular and peripheral vascular diseases. The authors review experimental results obtained from both animal studies and recent clinical trials, which point to the importance of EPCs potential as diagnostic markers and therapeutic tools in ischemic diseases. Furthermore, the article discusses the risk of potentially harmful side effects of altered EPCs number and functional properties, a critical barrier to overcome while bringing progenitor cell therapy to the clinical arena.

Endothelium, Vascular↗

PubMed2006

[Erythropoietin as a protective agent in myocardial ischemia].

Erythropoietin and its receptor, a cytokine hormone long-known for its pro-erythropoietic effect, has been found to be expressed on a variety of tissues, including the cardiovascular system. Recent experimental studies in the ischemia-reperfusion model have demonstrated that erythropoietin has a significant cardioprotective and pro-angiogenic effect. This effect is quantified by a reduction in the relative infarct and apoptosis area and improved recovery of mechanical function. Despite potentially detrimental effects, erythropoietin has been used extensively in the last decade for treatment of anemia associated with chronic renal failure, and it has been found to be a safe drug in humans. The potential role of erythropoietin in the treatment of ischemic heart disease in humans has yet to be demonstrated in preliminary clinical trials.

Anemia↗

PubMed2006

Neurohormonal and inflammatory markers as predictors of short-term outcome in patients with heart failure and cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy is a modality with proven morbidity and mortality benefit in advanced systolic heart failure. Nevertheless, not all patients respond favorably to CRT. Natriuretic peptides and inflammatory markers are elevated in congestive heart failure and reflect disease severity. OBJECTIVES: To test whether an early change in neurohormonal and inflammatory markers after implantation can predict the clinical response to CRT. METHODS: The study group included 32 patients with advanced symptomatic systolic heart failure and a prolonged QRS complex who were assigned to undergo CRT. Baseline plasma levels of B-type natriuretic peptide and high sensitivity C-reactive protein were determined in the peripheral venous blood and coronary sinus, Post-implantation levels were determined 2 weeks post-procedure in the PVB. Baseline levels and their change in 2 weeks were correlated with all-cause mortality and hospitalization for congestive heart failure. RESULTS: At baseline, coronary sinus levels of BNP but not hsCRP were significantly elevated compared to the PVB. Compared to baseline levels, BNP and hsCRP decreased significantly within 2 weeks after the implantation (BNP mean difference 229.1 +/- 102.5 pg/ml, 95% confidence interval 24.2-434, P< 0.0001; hsCRP mean difference 5.2 +/- 2.4 mg/dl, 95% CI 0.3-10.1, P= 0.001). During a mean follow-up of 17.7 +/- 8.2 months 6 patients died (18.7%) and 12 (37.5%) were hospitalized due to exacerbation of CHF. Baseline New York Heart Association and CSBNP levels predicted CHF-related hospitalizations. HsCRP levels or their change over 2 weeks did not predict all-cause mortality or hospitalizations. CONCLUSIONS: BNP levels in the CS and peripheral venous blood during biventricular implantation and 2 weeks afterwards predict clinical response and may guide patient management.

Acute Disease↗

PubMed2005

Transfer of endothelial progenitor and bone marrow cells influences atherosclerotic plaque size and composition in apolipoprotein E knockout mice.

OBJECTIVE: Recent clinical trials use cell therapy with bone marrow (BM) cells or endothelial progenitor cells (EPCs) for ischemic syndromes. We explored the effect of BM cell- or spleen cell-derived EPC transfer on plaque size and stability markers in the apolipoprotein E knockout (apoE KO) mouse model. METHODS AND RESULTS: ApoE KO mice aged 10 weeks served as recipients. Labeled BM cells and spleen cell-derived EPCs from age-matched apoE KO mice were injected intravenously to 2 groups of recipient mice each. Additional mice served as controls receiving saline. Both protocols were repeated 3 times at 2 weekly intervals. On killing, plaque size and character were studied, lipid profile analyzed, and serum and aortic cytokines assayed. Spleen cell-derived cells contained a significantly larger number of endothelial cell precursors. Labeled EPCs and BM cells were found abundantly in the spleens, yet also in the lesions of the recipient mice. Aortic sinus lesion size was significantly increased in mice receiving BM cells (n=10) in the EPC-treated group (n=10) compared with controls (n=10; a 54% and a 34% increase in aortic sinus plaque area, respectively). Mice receiving EPCs exhibited plaques with larger lipid cores and thinner fibrous caps and a higher number of infiltrating CD3 cells. RT-PCR analysis of aortas revealed reduced expression of mRNA for interleukin-10 (IL-10) in both cell transfer groups. Higher serum concentrations of IL-6 and monocyte chemoattractant protein-1 were found in sera from BM recipients, whereas lower IL-10 levels were found in mice transfused with spleen-derived EPCs. CONCLUSIONS: Transfer of BM cells and EPCs may result in an increase in atherosclerotic lesion size, whereas EPC transfer could also potentially influence plaque stability.

Animals↗

PubMed2005

Usefulness of anti-oxidized LDL antibody determination for assessment of clinical control in patients with heart failure.

BACKGROUND: It has been suggested that oxidative stress may play a role in the pathogenesis of heart failure, this may have potential implications for therapeutic strategies. However, measures of oxidative stress are subject to confounding inaccuracies. IgG antibodies to oxidized LDL reflect exposure to the lipoprotein over an extended period and may thus mirror oxidative stress over a prolonged time frame. Therefore, we tested the hypothesis that anti-oxLDL antibodies correlate with the control of heart failure (HF), as manifested by hospital admissions for cardiac dysfunction. METHODS: One hundred and two consecutive patients attending the HF clinic with either systolic or diastolic HF were enrolled and the quality of clinical control was evaluated by assessing hospital admissions over the year prior to index determination of the oxidative stress marker. Antibodies to oxLDL were determined by ELISA and pro-BNP levels were also measured. RESULTS: Most patients (mean age 71.5 years) had systolic HF; mean NYHA functional class was 2.7 and mean left ventricular ejection fraction was 39.7%. Anti-oxLDL antibodies, but not pro-BNP, correlated significantly with mean NYHA score (averaged from all clinic visits in the year prior to blood testing), and with hospital admissions over the year prior to blood testing. Mean IgG anti-oxLDL antibody levels in patients with hospital admissions were 3.4 times higher than those in subjects not hospitalized over the previous year. CONCLUSION: IgG anti-oxLDL antibody levels correlate with the severity of HF.

Aged↗