IC and EC injection of MSCs post-MI resulted in increased engraftment within infarcted tissue when compared with IV infusion, and IC was more efficient than EC. However, IC delivery was also associated with a higher incidence of decreased coronary blood flow. EC delivery into acutely infarcted myocardial tissue was safe and well tolerated and was associated with decreased remote organ engraftment with compared with IC and IV deliveries.
Coronary artery disease is responsible for much mortality and morbidity around the world. Platelets are involved in atherosclerotic disease development and the reduction of platelet activity by medications reduces the incidence and severity of disease. Red wine and grapes contain polyphenolic compounds, including flavonoids, which can reduce platelet aggregation and have been associated with lower rates of cardiovascular disease. Citrus fruits contain different classes of polyphenolics that may not share the same properties. This study evaluated whether commercial grape, orange and grapefruit juices, taken daily, reduce ex vivo platelet activity. In a randomized cross-over design, ten healthy human subjects (ages 26-58 y, five of each gender) drank 5-7.5 mL/(kg. d) of purple grape juice, orange juice or grapefruit juice for 7-10 d each. Platelet aggregation (whole blood impedance aggregometry, Chronolog Model #590) at baseline was compared to results after consumption of each juice. Drinking purple grape juice for one week reduced the whole blood platelet aggregation response to 1 mg/L of collagen by 77% (from 17.9 +/- 2.3 to 4.0 +/- 6.8 ohms, P = 0.0002). Orange juice and grapefruit juice had no effect on platelet aggregation. The purple grape juice had approximately three times the total polyphenolic concentration of the citrus juices and was a potent platelet inhibitor in healthy subjects while the citrus juices showed no effect. The platelet inhibitory effect of the flavonoids in grape juice may decrease the risk of coronary thrombosis and myocardial infarction.
Abstract-Inwardly rectifying Kϩ (Kir) channels are responsible for maintaining endothelial membrane potential and play a key role in endothelium-dependent vasorelaxation. In this study, we show that endothelial Kir channels are suppressed by hypercholesterolemic levels of lipoproteins in vitro and by serum hypercholesterolemia in vivo. Specifically, exposing human aortic endothelial cells to acetylated low-density lipoprotein or very low density lipoprotein resulted in a time-and concentration-dependent decrease in Kir current that correlated with the degree of cholesterol loading. The suppression was fully reversible by cholesterol depletion. Furthermore, a decrease in Kir current resulted in depolarization of endothelial membrane potential. Most important, the flow sensitivity of Kir currents was also impaired by cholesterol loading. Specifically, flow-induced increase in Kir current was suppressed by 70%, and flow-induced hyperpolarization was almost completely abrogated. Furthermore, we show that hypercholesterolemia in vivo also strongly suppresses endothelial Kir currents and causes a shift in endothelial membrane potential, as determined by comparing the currents in aortic endothelial cells freshly isolated from healthy or hypercholesterolemic pigs. Therefore, we suggest that suppression of Kir current is one of the important factors in hypercholesterolemia-induced endothelial dysfunction. (Circ Res. 2006;98:1064-1071.) Key Words: K channels Ⅲ cholesterol Ⅲ lipoproteins Ⅲ flow Ⅲ vasodilatation N umerous studies have shown that a major risk factor for the development of cardiovascular disease is plasma hypercholesterolemia, elevation of low-and very low-density lipoproteins (LDL and VLDL), as well as the oxidized modification of LDL, oxidized LDL (oxLDL). 1,2 Endothelial dysfunction develops in the early stages of cardiovascular disease and is a strong predictor of its development. 3 A hallmark of endothelial dysfunction in vivo is impairment of flow-mediated vasodilatation (FMV). Indeed, several studies have shown that plasma hypercholesterolemia impairs FMV both in humans and in animal models of atherosclerosis. 4,5 However, molecular mechanisms that underlie hypercholesterolemia-induced endothelial dysfunction are poorly understood.Our studies focus on the impact of hypercholesterolemia on endothelial inwardly rectifying K ϩ (Kir) channels, the major determinants of endothelial membrane potential 6,7 and putative flow sensors. 8 -10 The resting membrane potential in endothelial cells ranges between approximately Ϫ30 and Ϫ80 mV depending on a specific endothelial cell type. 7 Aortic endothelial cells typically have resting potentials in a strongly hyperpolarizing range (approximately Ϫ60 mV/Ϫ80 mV) both in culture 8,[11][12][13] and in intact aortas, 14 consistent with a major contribution of K ϩ channels. Several types of K ϩ channels are expressed in endothelial cells: Kir channels that maintain stable membrane potential under resting condition and are responsible for flow-induced hyperpolarization an...
Grape products, rich in polyphenolics, inhibit platelet aggregation (PA), a risk factor for coronary artery disease. We postulated that combining extracts of grape seed (GSD) and grape skin (GSK), primary sources of grape polyphenolics, individually shown to inhibit PA, might enhance their individual antiplatelet effects. This hypothesis was examined in vitro (human platelets) and ex vivo (dog platelets) by studying the effects of the extracts on collagen-induced whole blood PA. In vitro, threshold concentration of only GSD, individually incubated with blood, significantly inhibited PA; PA was inhibited by 12.7 +/- 3.5% (P < or = 0.01). No significant changes in Pa were observed with threshold concentrations of GSK, used individually. In two dose combinations, GSD and GSK inhibited PA 40.5 +/- 10.1% (P < or = 0.005) and 96.5 +/- 3.1% (P < or = 0.001). In the ex vivo study, seven dogs were fed threshold doses of GSD or GSK individually, in combination or in combination with a proprietary enzyme blend (EB; thought to enhance bioavailability) for 8 d. PA was measured before and after each treatment. PA measurements were also repeated 24 h after the final dose of GSD + GSK + EB. Feeding the extracts individually did not affect PA, whereas feeding them in combination inhibited PA by 31.9 +/- 7.1% (P < or = 0.05). Feeding EB in addition to GSD + GSK inhibited PA by 56.2 +/- 8.1% (P < or = 0.005); 24 h later, PA was still inhibited by 31.5 +/- 10.5% (P < or = 0.05), suggesting a residual antiplatelet effect from the administration of the final dose. The results suggest that the components of GSD and GSK, when present in combination as in red wine, grape juice or in a commercial preparation containing both extracts, exhibit a greater antiplatelet effect than when present individually.
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