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Biomedical subjects

Michael Böhm

Publications and source records attributed to Michael Böhm.

At least 37 records · Page 2Linked to original sources
PubMed2006

A review of homocysteine and heart failure.

Chronic heart failure (CHF) is a major public health problem causing considerable morbidity and mortality. Recently, plasma homocysteine (HCY) has been suggested to be increased in CHF patients potentially representing a newly recognized risk marker. This manuscript reviews the existing literature regarding hyperhomocysteinemia (HHCY) and CHF. Clinical data indicate that HHCY is associated with an increased incidence of CHF as well as with the severity of the disease. Mechanistic studies of HHCY and CHF are rare. However, preliminary results suggest that HHCY causes adverse cardiac remodelling characterized by interstitial and perivascular fibrosis resulting in increased myocardial stiffness. In addition, HHCY seems to affect the pump function of the myocardium. The mechanisms leading from an elevated HCY level to reduced pump function and adverse cardiac remodelling are a matter of speculation. Existing data indicate that direct effects of HCY on the myocardium as well as NO independent vascular effects are involved. In conclusion, HHCY might be a potential aetiological factor in CHF. Future studies need to clarify the mechanistic role of HHCY in CHF as a useful paradigm with most interesting therapeutic implications, because HCY lowering therapy could favourably influence the prognosis in CHF patients.

Cardiac Output, Low↗
PubMed2006

Uptake of cardiovascular drugs into the human heart: expression, regulation, and function of the carnitine transporter OCTN2 (SLC22A5).

BACKGROUND: To date, the uptake of drugs into the human heart by transport proteins is poorly understood. A candidate protein is the organic cation transporter novel type 2 (OCTN2) (SLC22A5), physiologically acting as a sodium-dependent transport protein for carnitine. We investigated expression and localization of OCTN2 in the human heart, uptake of drugs by OCTN2, and functional coupling of OCTN2 with the eliminating ATP-binding cassette (ABC) transporter ABCB1 (P-glycoprotein). METHODS AND RESULTS: Messenger RNA levels of OCTN2 and ABCB1 were analyzed in heart samples by quantitative polymerase chain reaction. OCTN2 was expressed in all auricular samples that showed a pronounced interindividual variability (35 to 1352 copies per 20 ng of RNA). Although a single-nucleotide polymorphism in OCTN2 (G/C at position -207 of the promoter) had no influence on expression, administration of beta-blockers resulted in significantly increased expression. Localization of OCTN2 by in situ hybridization, laser microdissection, and immunofluorescence microscopy revealed expression of OCTN2 mainly in endothelial cells. For functional studies, OCTN2 was expressed in Madin-Darby canine kidney (MDCKII) cells. Using this system, verapamil, spironolactone, and mildronate were characterized both as inhibitors (EC50=25, 26, and 21 micromol/L, respectively) and as substrates. Like OCTN2, ABCB1 was expressed preferentially in endothelial cells. A significant correlation of OCTN2 and ABCB1 expression in the human heart was observed, which suggests functional coupling. Therefore, the interaction of OCTN2 with ABCB1 was tested with double transfectants. This approach resulted in a significantly higher transcellular transport of verapamil, a substrate for both OCTN2 and ABCB1. CONCLUSIONS: OCTN2 is expressed in the human heart and can be modulated by drug administration. Moreover, OCTN2 can contribute to the cardiac uptake of cardiovascular drugs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

AT1 receptor antagonism improves endothelial dysfunction in postmenopausal women.

The menopause is associated with an increased incidence of atherosclerotic disease. Estrogen deficiency causes AT1 receptor overexpression which is involved in the development of vascular dysfunction. The effect of a 6 week-treatment with the AT1 receptor antagonist candesartan (16 mg/d) on endothelium-dependent vasorelaxation was compared to the treatment with placebo or the calcium channel antagonist felodipine (5 mg/d) in 29 postmenopausal women in the absence or presence of hormone replacement therapy (HRT) in a prospective, double-blind, randomized cross-over study. Endothelial function was assessed by measurement of forearm blood flow (FBF) by venous occlusion plethysmography. FBF during reactive hyperemia was significantly improved by candesartan in patients without HRT (hyperemic peak flow and area under the FBF curve), whereas felodipine and placebo exerted no effect. In patients with HRT, no treatment regimen showed a significant effect on endothelial function. Nitroglycerin-induced vasorelaxation and basal FBF were not significantly altered in all groups. AT1 receptor antagonism improves vascular function in postmenopausal women without HRT. Thus, AT1 receptor blockade may resemble an efficient approach for the prevention of vascular dysfunction in estrogen-deficient women.

Aged↗
PubMed2006

ACE inhibition in secondary prevention: are the results controversial?

Results from the HOPE and EUROPA trials showed that ACE inhibitors lower cardiovascular mortality of patients with atherosclerosis and preserved left ventricular function. However, despite apparently adequate study design, the recently conducted PEACE trial detected no benefit of an additional ACE inhibitor treatment in patients with coronary artery disease and no heart failure with respect to cardiovascular risk reduction. One of the main reasons for this discrepancy might be the lower cardiovascular baseline risk of the PEACE study population, which was more intensively treated with lipid lowering drugs and myocardial revascularization prior to enrollment than patients in HOPE or EUROPA. Another reason for the negative results of PEACE might be substance-specific differences between individual ACE inhibitors (trandolapril in PEACE, ramipril in HOPE, and perindopril in EUROPA) in their clinical efficacy to reduce cardiovascular end-points. The PEACE trial did not achieve the originally projected sample size and the addition of a soft end-point of revascularization has not been helpful. While the results from the PEACE trial suggest that low-risk patients with coronary artery disease and with preserved left ventricular function who receive intensive standard therapy including lipid lowering and coronary revascularization may not benefit from additional ACE inhibition therapy, this conclusion should be made with caution. A number of reasons, other than drug treatment efficacy, may explain the neutral results in the PEACE trial. Further studies are needed to try to resolve this issue. In the meantime, the overwhelming data still support the use of ACE inhibitors in patients with coronary artery disease with preserved left ventricular function.

Angioplasty, Balloon, Coronary↗
PubMed2006

Organic anion transporting polypeptide 2B1 is a high-affinity transporter for atorvastatin and is expressed in the human heart.

BACKGROUND: The cardiac effects of statins are subject to controversial discussion, and the mechanism of their uptake into the human heart is unknown. A candidate protein is the organic anion transporting polypeptide (OATP) 2B1 (SLCO2B1), because related transporters are involved in the uptake of statins into the human liver. In this study we examine OATP2B1 expression in the human heart and describe statins as inhibitors and substrates of OATP2B1. METHODS: The expression of OATP2B1 was analyzed in 46 human atrial and 15 ventricular samples, including samples from hearts with dilated cardiomyopathy and hearts with ischemic cardiomyopathy. RESULTS: Significant messenger ribonucleic acid expression was found in all samples, with no difference in the diseased hearts. However, patients who had taken atorvastatin exhibit decreased OATP2B1 messenger ribonucleic acid expression compared with patients with no statin treatment. OATP2B1 protein was detected at approximately 85 kd in atrial samples, as well as ventricular samples, and could be localized to the vascular endothelium. Furthermore, estrone-3-sulfate transport into OATP2B1-overexpressing Madin-Darby canine kidney II cells was inhibited by various drugs, including atorvastatin, simvastatin, cerivastatin, glyburide (INN, glibenclamide), and gemfibrozil, with the most pronounced effect being found for atorvastatin (inhibition constant, 0.7 +/- 0.4 micromol/L). Whereas simvastatin (lactone) itself was not transported by OATP2B1, atorvastatin was identified as a high-affinity substrate for OATP2B1 (Michaelis-Menten constant, 0.2 micromol/L) by direct transport measurement via liquid chromatography-tandem mass spectrometry. CONCLUSION: OATP2B1 is a high-affinity uptake transporter for atorvastatin and is expressed in the vascular endothelium of the human heart, suggesting its involvement in cardiac uptake of atorvastatin.

Aged↗
PubMed2006

In vitro comparison of aortic valve movement after valve-preserving aortic replacement.

OBJECTIVE: In aortic valve regurgitation and aortic dilatation, preservation of the aortic valve is possible by means of root remodeling (Yacoub procedure) or valve reimplantation (David procedure). In vivo studies suggest that reimplantation might substantially influence aortic valve-motion characteristics. Evaluation of aortic valve movement in vivo, however, is technically limited and is difficult to standardize. We evaluated the aortic valve-motion pattern echocardiographically in vitro after reimplantation and remodeling. METHODS: By using aortic roots of house pigs (aortoventricular diameter, 22 mm) a Yacoub procedure (22-mm graft; group Y, n = 5) or a David I procedure (24-mm graft; group D, n = 5) was performed. Roots after supracommissural replacement (22-mm graft; group C, n = 5) served as control valves. In an electrohydraulic, computer-controlled pulse duplicator the valves were tested at flows of 2, 4, 7, and 9 L/min. Echocardiographically assessed parameters were rapid valve-opening velocity, slow valve-closing velocity, rapid valve-closing velocity, rapid valve-opening time, rapid valve-closing time, ejection time, maximum valve opening, slow valve-closing displacement, and maximum flow velocity. RESULTS: Mean rapid valve-opening velocity and mean rapid valve-closing velocity at a cardiac output of 2 to 9 L/min were fastest in group D (rapid valve-opening velocity: 69 +/- 10 cm/s [group D] vs 39 +/- 4 cm/s [group Y] vs 42 +/- 4 cm/s [group C], P = .0041; rapid valve-closing velocity: 22 +/- 2 cm/s [group D] vs 16 +/- 2 cm/s [group Y] vs 17 +/- 1 cm/s [group C], P = .0272), and slow valve-closing velocity was slowest in group D (0.2 +/- 0.1 cm/s [group D] vs 1.0 +/- 0.3 cm/s [group Y] vs 0.6 +/- 0.1 cm/s [group C], P = .0063). With increasing cardiac output, the difference in rapid valve-opening velocity between the groups increased, the difference in slow valve-closing velocity remained unchanged, and the difference in rapid valve-closing velocity decreased. CONCLUSIONS: In this standardized experimental setting remodeling of the aortic valve provides significantly smoother valve movements. This might contribute to preservation of a better valve performance during long-term follow-up.

Animals↗
PubMed2006

Telmisartan inhibits beta2-integrin MAC-1 expression in human T-lymphocytes.

OBJECTIVE: The pathogenesis of atherosclerosis, a chronic inflammatory disease, is influenced by the renin-angiotensin system and especially by angiotensin II subtype 1 (AT1) receptor activation. Although pro-inflammatory properties of angiotensin II as well as anti-inflammatory effects of AT1 receptor antagonists are well known, the underlying mechanisms are poorly understood. METHOD AND RESULTS: In a prospective double-blind study, patients with hypertension and coronary artery disease were treated with either 40 mg telmisartan (n = 21) or placebo (n = 21) for 12 weeks. General markers of inflammation, such as high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6), and cell adhesion molecules, such as soluble intercellular adhesion molecule (s-ICAM-1) and the leucocyte adhesion molecule soluble-L-selectin (sL-selectin), as well as the lymphocytic expression of the beta2 integrin MAC-1, were assessed before and after treatment. Telmisartan therapy significantly decreased the lymphocyte beta2 integrin MAC-1 expression, whereas hs-CRP, IL-6, s-ICAM and sL-selectin remained unaltered. In-vitro experiments were conducted to clarify the mode of action. Cultured human lymphocytes were stimulated with either angiotensin II or phorbol-12-myristate-13-acetate (PMA)/ionomycin, alone or after pretreatment with telmisartan. Whereas angiotensin II exerted no effect on beta2-integrin MAC-1 expression in lymphocytes, telmisartan dose-dependently inhibited beta2-integrin expression in lymphocytes in the absence or presence of angiotensin II. CONCLUSION: The AT1 receptor antagonist telmisartan inhibits the expression of the pro-inflammatory beta2-integrin MAC-1 expression in lymphocytes independently of angiotensin II, suggesting an AT1 receptor-independent atheroprotective effect of this AT1 receptor antagonist.

Aged↗
PubMed2006

Blood pressure reduction with olmesartan in mild-to-moderate essential hypertension: a planned interim analysis of an open label sub-study in German patients.

OBJECTIVE: To present the baseline characteristics and open-label treatment phase results for German patients in OLMEBEST, a European, multinational, partially randomized, partially double-blind study in patients with mild-to-moderate essential hypertension. RESEARCH DESIGN AND METHODS: After a 2-week placebo run-in, patients received olmesartan 20 mg for 8 weeks. Controlled patients (mean sitting diastolic blood pressure [sDBP] < 90 mmHg) continued on olmesartan 20 mg/day for a further 4 weeks. Non-controlled patients (sDBP > 90 mmHg) were randomized to olmesartan 40 mg/day or olmesartan 20 mg/day plus 12.5 mg hydrochlorothiazide for 4 weeks. Of 823 patients included, 558 continued olmesartan 20 mg treatment and 228 patients were randomized to olmesartan 40 mg/day or combination therapy. Efficacy variables included the change from baseline in mean sitting DBP and systolic blood pressure [sSBP] at Week 8 (and Week 12 for controlled patients), and the proportion of controlled patients and responders (mean sDBP < 90 mmHg or improvement of > 10 mmHg from baseline at Week 8). RESULTS: After 8 weeks of olmesartan medoxomil 20 mg, mean reduction from baseline in sDBP was 11.8 mmHg and in sSBP was 17.1 mmHg. In controlled patients continuing open-label olmesartan medoxomil 20 mg, mean reduction from baseline at 12 weeks in sDBP was 14.9 mmHg and in sSBP was 20.1 mmHg. At Week 8, the response rate was 76% and the control rate was 70%. Olmesartan medoxomil 20 mg/day was well tolerated; 30.9% of patients experienced an adverse event, and the majority of these events were judged by the investigators to be mild. CONCLUSION: Olmesartan medoxomil monotherapy at the recommended dosage of 20 mg once daily is effective and well tolerated in patients with mild-to-moderate hypertension.

Adolescent↗
PubMed2006

Statins in the treatment of chronic heart failure: a systematic review.

BACKGROUND: The efficacy of statin therapy in patients with established chronic heart failure (CHF) is a subject of much debate. METHODS AND FINDINGS: We conducted three systematic literature searches to assess the evidence supporting the prescription of statins in CHF. First, we investigated the participation of CHF patients in randomized placebo-controlled clinical trials designed to evaluate the efficacy of statins in reducing major cardiovascular events and mortality. Second, we assessed the association between serum cholesterol and outcome in CHF. Finally, we evaluated the ability of statin treatment to modify surrogate endpoint parameters in CHF. Using validated search strategies, we systematically searched PubMed for our three queries. In addition, we searched the reference lists from eligible studies, used the "see related articles" feature for key publications in PubMed, consulted the Cochrane Library, and searched the ISI Web of Knowledge for papers citing key publications. Search 1 resulted in the retrieval of 47 placebo-controlled clinical statin trials involving more than 100,000 patients. CHF patients had, however, been systematically excluded from these trials. Search 2 resulted in the retrieval of eight studies assessing the relationship between cholesterol levels and outcome in CHF patients. Lower serum cholesterol was consistently associated with increased mortality. Search 3 resulted in the retrieval of 18 studies on the efficacy of statin treatment in CHF. On the whole, these studies reported favorable outcomes for almost all surrogate endpoints. CONCLUSIONS: Since CHF patients have been systematically excluded from randomized, controlled clinical cholesterol-lowering trials, the effect of statin therapy in these patients remains to be established. Currently, two large, randomized, placebo-controlled statin trials are under way to evaluate the efficacy of statin treatment in terms of reducing clinical endpoints in CHF patients in particular.

Anticholesteremic Agents↗
PubMed2006

HMG-CoA reductase inhibitors in chronic heart failure: potential mechanisms of benefit and risk.

HMG-CoA reductase inhibitors (statins) have been shown to reduce mortality and cardiovascular morbidity in patients with hyperlipidaemia and those with coronary artery disease. However, evidence for statin treatment in patients with chronic heart failure (CHF) remains a subject of debate. Patients with heart failure were generally excluded in the existing trials and a different patient population with a distinct pattern of morbidity and treatment was studied. In addition, no safety data are available for statins in patients with heart failure, where there are potential concerns about coenzyme Q10 depletion and excessive low-density lipoprotein reduction. This review summarises the clinical and preclinical evidence for potential beneficial effects of statins in CHF. In experimental systems, statins have been shown to improve cardiac function through antioxidative and anti-inflammatory action. Statins improve endothelial function, may reduce neurohormonal activation, and stimulate endothelial progenitor cells. Some of these effects occur independently of cholesterol lowering and can be explained by inhibition of isoprenylation of signal transducing proteins of the family of Rho guanosine triphosphatases. Two ongoing controlled randomised trials (CORONA [Controlled Rosuvastatin Multinational Study in Heart Failure] and GISSI-HF [Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico--Heart Failure]) will help us to assess whether the described beneficial effects of statins in heart failure outweigh the potential negative effects and translate into the reduction of clinical endpoints.

Animals↗
PubMed2006

Hyperhomocysteinemia--the biochemical link between a weak heart and brittle bones?

Osteoporosis, chronic heart failure (CHF) and mild to moderate hyperhomocysteinemia (HHCY) can frequently be found in elderly individuals and often occur in the same individual. Due to demographic changes in the number of elderly people the total number of individuals suffering from osteoporosis and/or CHF, and hence the cost to society, will increase dramatically over the next 50 years. Thus, prevention of these diseases by identifying and modifying risk factors is a major issue. Recent large population-based prospective studies suggested HHCY as an independent risk factor for CHF and osteoporosis. However, the mechanisms that link HHCY to CHF and osteoporosis are almost unknown. Moreover, until now both diseases have been considered as independent diseases. The finding that heart and bones share a common biochemical risk factor raises the question if there is a biochemical link between these two diseases? This manuscript reviews the existing literature about HHCY and osteoporosis, about HHCY and CHF, and about possible mechanisms that link HHCY to both diseases. Existing data suggest that HHCY could be a useful paradigm with most interesting therapeutic implications, because HCY lowering therapy could favourably influence the course in CHF and osteoporotic patients.

Animals↗
PubMed2005

Sildenafil in the treatment of Raynaud's phenomenon resistant to vasodilatory therapy.

BACKGROUND: Vasodilatory therapy of Raynaud's phenomenon represents a difficult clinical problem because treatment often remains inefficient and may be not tolerated because of side effects. METHODS AND RESULTS: To investigate the effects of sildenafil on symptoms and capillary perfusion in patients with Raynaud's phenomenon, we performed a double-blinded, placebo-controlled, fixed-dose, crossover study in 16 patients with symptomatic secondary Raynaud's phenomenon resistant to vasodilatory therapy. Patients were treated with 50 mg sildenafil or placebo twice daily for 4 weeks. Symptoms were assessed by diary cards including a 10-point Raynaud's Condition Score. Capillary flow velocity was measured in digital nailfold capillaries by means of a laser Doppler anemometer. While taking sildenafil, the mean frequency of Raynaud attacks was significantly lower (35+/-14 versus 52+/-18, P=0.0064), the cumulative attack duration was significantly shorter (581+/-133 versus 1046+/-245 minutes, P=0.0038), and the mean Raynaud's Condition Score was significantly lower (2.2+/-0.4 versus 3.0+/-0.5, P=0.0386). Capillary blood flow velocity increased in each individual patient, and the mean capillary flow velocity of all patients more than quadrupled after treatment with sildenafil (0.53+/-0.09 versus 0.13+/-0.02 mm/s, P=0.0004). Two patients reported side effects leading to discontinuation of the study drug. CONCLUSIONS: Sildenafil is an effective and well-tolerated treatment in patients with Raynaud's phenomenon.

Adult↗
PubMed2005

Continuous aortic flow augmentation: a pilot study of hemodynamic and renal responses to a novel percutaneous intervention in decompensated heart failure.

BACKGROUND: Diminished aortic flow may induce adverse downstream vascular and renal signals. Investigations in a heart failure animal model have shown that continuous aortic flow augmentation (CAFA) achieves hemodynamic improvement and ventricular unloading, which suggests a novel therapeutic approach to patients with heart failure exacerbation that is inadequately responsive to medical therapy. METHODS AND RESULTS: We studied 24 patients (12 in Europe and 12 in the United States) with heart failure exacerbation and persistent hemodynamic derangement despite intravenous diuretic and inotropic and/or vasodilator treatment. CAFA (mean+/-SD 1.34+/-0.12 L/min) was achieved through percutaneous (n=19) or surgical (n=5) insertion of the Cancion system, which consists of inflow and outflow cannulas and a magnetically levitated and driven centrifugal pump. Hemodynamic improvement was observed within 1 hour. Systemic vascular resistance decreased from 1413+/-453 to 1136+/-381 dyne.s.cm(-5) at 72 hours (P=0.0008). Pulmonary capillary wedge pressure decreased from 28.5+/-4.9 to 19.8+/-7.0 mm Hg (P<0.0001), and cardiac index (excluding augmented aortic flow) increased from 1.97+/-0.44 to 2.27+/-0.43 L.min(-1).m(-2) (P=0.0013). Serum creatinine trended downward during treatment (overall P=0.095). There were 8 complications during treatment, 7 of which were self-limited. Hemodynamics remained improved 24 hours after CAFA discontinuation. CONCLUSIONS: In patients with heart failure and persistent hemodynamic derangement despite intravenous inotropic and/or vasodilator therapy, CAFA improved hemodynamics, with a reduction in serum creatinine. CAFA represents a promising, novel mode of treatment for patients who are inadequately responsive to medical therapy. The clinical impact of the observed hemodynamic improvement is currently being explored in a prospective, randomized, controlled trial.

Adult↗
PubMed2005

Outpatient electrical cardioversion of atrial fibrillation: efficacy, safety and patients' quality of life.

BACKGROUND: Atrial fibrillation (AF) is the most common sustained arrhythmia. To lower costs and to reduce hospitalization electrical cardioversion (CV) is frequently performed in an outpatient setting although data on safety and patient-acceptance are sparse. Aims of this study were to fill this gap by evaluating efficacy, complication rate, quality of life after CV and patient-acceptance of outpatient CV. METHODS: One-hundred and eleven consecutive patients with persistent AF were included. Patients were under continuous monitoring throughout the procedure and 3 h after. CV was done in deep sedation using rising energies (200->360 J). Quality of life (QoL), late adverse events and patient-acceptance were assessed 4 weeks after CV. RESULTS: AF could be terminated with a mean of 1.4 shocks in all patients. Acute adverse events could be observed in 3.6%. Late adverse events were noted in 8.2%. Seventy-four percent of the patients felt "good" or "very good" the day of CV. Eighty-nine percent of the patients would undergo a CV again and in case of a further CV 69% of the patients would prefer an outpatient setting. Patients with a lower QoL-classification had longer duration of atrial fibrillation (median 1 vs. 3 months, p<0.05). No other clinical predictor for adverse events or a low QoL-classification could be identified. CONCLUSION: Electrical CV of persistent AF in an outpatient setting is feasible, safe and has a high patient-acceptance.

Aged↗
PubMed2005

Circulating endothelial progenitor cells and cardiovascular outcomes.

BACKGROUND: Endothelial progenitor cells derived from bone marrow are believed to support the integrity of the vascular endothelium. The number and function of endothelial progenitor cells correlate inversely with cardiovascular risk factors, but the prognostic value associated with circulating endothelial progenitor cells has not been defined. METHODS: The number of endothelial progenitor cells positive for CD34 and kinase insert domain receptor (KDR) was determined with the use of flow cytometry in 519 patients with coronary artery disease as confirmed on angiography. After 12 months, we evaluated the association between baseline levels of endothelial progenitor cells and death from cardiovascular causes, the occurrence of a first major cardiovascular event (myocardial infarction, hospitalization, revascularization, or death from cardiovascular causes), revascularization, hospitalization, and death from all causes. RESULTS: A total of 43 participants died, 23 from cardiovascular causes. A first major cardiovascular event occurred in 214 patients. The cumulative event-free survival rate increased stepwise across three increasing baseline levels of endothelial progenitor cells in an analysis of death from cardiovascular causes, a first major cardiovascular event, revascularization, and hospitalization. After adjustment for age, sex, vascular risk factors, and other relevant variables, increased levels of endothelial progenitor cells were associated with a reduced risk of death from cardiovascular causes (hazard ratio, 0.31; 95 percent confidence interval, 0.16 to 0.63; P=0.001), a first major cardiovascular event (hazard ratio, 0.74; 95 percent confidence interval, 0.62 to 0.89; P=0.002), revascularization (hazard ratio, 0.77; 95 percent confidence interval, 0.62 to 0.95; P=0.02), and hospitalization (hazard ratio, 0.76; 95 percent confidence interval, 0.63 to 0.94; P=0.01). Endothelial progenitor-cell levels were not predictive of myocardial infarction or of death from all causes. CONCLUSIONS: The level of circulating CD34+KDR+ endothelial progenitor cells predicts the occurrence of cardiovascular events and death from cardiovascular causes and may help to identify patients at increased cardiovascular risk.

Aged↗
PubMed2005

The ATP-binding cassette transporter ABCG2 (BCRP), a marker for side population stem cells, is expressed in human heart.

Efforts to improve severely impaired myocardial function include transplantation of autologous hematopoietic side population (SP) stem cells. The transmembrane ABC-type (ATP binding cassette) half-transporter ABCG2 (BCRP) serves as a marker protein for SP cell selection. We have recently shown that other ABC transport proteins such as ABCB1 and ABCC5 are differentially expressed in normal and diseased human heart. Here we investigated localization and individual ABCG2 expression in 15 ventricular (including 10 cardiomyopathic) and 51 auricular heart tissue samples using immunohistochemistry, confocal laser scanning fluorescence microscopy, and real-time RT-PCR. Individual genotypes were assigned using PCR-restriction fragment length polymorphism (RFLP) analysis and subsequently correlated to ABCG2 mRNA levels. ABCG2 was localized in endothelial cells of capillaries and arterioles of all samples. Ventricular samples from cardiomyopathic hearts exhibited significantly increased levels of ABCG2 mRNA (ABCG2/18S rRNA: 1.08 +/- 0.30 x 10(-7); p=0.028 (dilative cardiomyopathy) and 1.16 +/- 0.46 x 10(-7); p=0.009 (ischemic cardiomyopathy) compared with 0.44 +/- 0.26 x 10(-7) in nonfailing hearts). The individual haplotypes were not associated with altered mRNA expression. ABCG2 is variably expressed in endothelial cells of human heart, where it may function as a protective barrier against cardiotoxic drugs such as anthracyclines or mitoxantrone. ABCG2 expression is induced in dilative and ischemic cardiomyopathies.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed2005

Stem cells in the dog heart are self-renewing, clonogenic, and multipotent and regenerate infarcted myocardium, improving cardiac function.

The purpose of this study was to determine whether the heart in large mammals contains cardiac progenitor cells that regulate organ homeostasis and regenerate dead myocardium after infarction. We report that the dog heart possesses a cardiac stem cell pool characterized by undifferentiated cells that are self-renewing, clonogenic, and multipotent. These clonogenic cells and early committed progeny possess a hepatocyte growth factor (HGF)-c-Met and an insulin-like growth factor 1 (IGF-1)-IGF-1 receptor system that can be activated to induce their migration, proliferation, and survival. Therefore, myocardial infarction was induced in chronically instrumented dogs implanted with sonomicrometric crystals in the region of the left ventricular wall supplied by the occluded left anterior descending coronary artery. After infarction, HGF and IGF-1 were injected intramyocardially to stimulate resident cardiac progenitor cells. This intervention led to the formation of myocytes and coronary vessels within the infarct. Newly generated myocytes expressed nuclear and cytoplasmic proteins specific of cardiomyocytes: MEF2C was detected in the nucleus, whereas alpha-sarcomeric actin, cardiac myosin heavy chain, troponin I, and alpha-actinin were identified in the cytoplasm. Connexin 43 and N-cadherin were also present. Myocardial reconstitution resulted in a marked recovery of contractile performance of the infarcted heart. In conclusion, the activation of resident primitive cells in the damaged dog heart can promote a significant restoration of dead tissue, which is paralleled by a progressive improvement in cardiac function. These results suggest that strategies capable of activating the growth reserve of the myocardium may be important in cardiac repair after ischemic injury.

Animals↗