Influence of beta-adrenoceptor blockade on the myocardial accumulation of fatty acid tracer and its intracellular metabolism in the heart after ischemia-reperfusion injury.
Second Department of Internal Medicine, Faculty of Medicine, University of Toyama, Toyama 930-0194, Japan. Circulation Journal
(Impact Factor: 3.94).
Increases in sympathetic nerve activity during ischemia may increase intracellular fatty acid (FA) accumulation via enhanced FA uptake and inhibition of beta-oxidation. Therefore, the beneficial effects of beta-adrenoceptor blockade on myocardial ischemic injury might result from the suppression of FA accumulation.
Carvedilol (1 mg/kg) or propranolol (1 mg/kg) was injected 10 min before 15-min occlusion of coronary artery in rats. Myocardial FA accumulation and intracellular metabolites of FA tracer were determined 3 days after reperfusion using (125)I-and (131)I-9-metylpentadecanoic acid (9MPA). Carvedilol significantly decreased 9MPA accumulation in both the ischemic region (IR) and non-IR, as compared with vehicle, and increased its clearance. However, the non-metabolized 9MPA fraction was not different between carvedilol- and vehicle-treated rats. Consequently, the amount of non-metabolized 9MPA in the myocardium was lower in rats treated with carvedilol than in those given vehicle. These effects of carvedilol were not different from those of propranolol.
Beta-adrenoceptor blockade did not affect a visual assessment of the autoradiographic image of 9MPA in hearts subjected to ischemia-reperfusion, but it accelerated the clearance of 9MPA in both the IR and non-IR. The administration of beta-blockade before ischemia could accelerate the recovery from ischemia-reperfusion injury by inhibiting myocardial FA accumulation before beta-oxidation.
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Available from: Fatemeh Hajighasemi
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ABSTRACT: Beta-adrenergic blocking agents have been broadly used for treatment of many cardiovascular diseases such as arterial hypertension and ischemic heart failure. Anti-tumoral, anti-inflammatory and anti-angiogenesis effects of propranolol (a non-selective beta-adrenergic blocker) have been shown. Angiogenesis (replenish of the pre-existing vascular networks) plays a critical role in some pathological conditions such as tumor expansion and metastasis. In this study, we investigated the effects of propranolol on vascular endothelial growth factor (VEGF) production and matrix metalloproteinase-2 (MMP-2) activity (two important angiogenic factors) in human leukemic cell lines in vitro.
Two human leukemic T (Molt-4 and Jurkat) and one monocyte (U937) cell lines were used in this study. The cells were cultured in complete RPMI medium and then incubated with different concentrations of propranolol (0.3-30 microM) in the presence or absence of phorbol myristate acetate (PMA, 25 ng/ml) for 48 hours. The level of VEGF secreted in the cell culture supernatants was measured with enzyme-linked immunosorbent assay kits (R and D systems) and MMP-2 activity in cell-conditioned media was evaluated by gelatin zymography.
Propranolol significantly decreased VEGF production and also MMP-2 activity in PMA-activated human leukemic cell lines Molt-4, Jurkat and U937 at 30 microM concentration of the drug compared to untreated control cells (P<0.05).
Propranolol might be a useful anti-angiogenic agent in hematopoietic malignancies. Thus, propranolol along with its chronic long-term usage in cardiac problems may have potential implication in treatment of leukemia.
Available from: John Ussher
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ABSTRACT: There is a constant high demand for energy to sustain the continuous contractile activity of the heart, which is met primarily by the beta-oxidation of long-chain fatty acids. The control of fatty acid beta-oxidation is complex and is aimed at ensuring that the supply and oxidation of the fatty acids is sufficient to meet the energy demands of the heart. The metabolism of fatty acids via beta-oxidation is not regulated in isolation; rather, it occurs in response to alterations in contractile work, the presence of competing substrates (i.e., glucose, lactate, ketones, amino acids), changes in hormonal milieu, and limitations in oxygen supply. Alterations in fatty acid metabolism can contribute to cardiac pathology. For instance, the excessive uptake and beta-oxidation of fatty acids in obesity and diabetes can compromise cardiac function. Furthermore, alterations in fatty acid beta-oxidation both during and after ischemia and in the failing heart can also contribute to cardiac pathology. This paper reviews the regulation of myocardial fatty acid beta-oxidation and how alterations in fatty acid beta-oxidation can contribute to heart disease. The implications of inhibiting fatty acid beta-oxidation as a potential novel therapeutic approach for the treatment of various forms of heart disease are also discussed.
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