COX-2 plays an important role in VEGF-induced angiogenesis via p38 and JNK kinase activation pathways. These findings suggest that the cardioprotective role of COX-2 may be, at least in part, through its angiogenic activity.

Background-Enhanced external counterpulsation (EECP) is a circulation assist device that may improve endothelial dysfunction by increasing shear stress. Chronic exposure of vascular endothelial cells and vascular smooth muscle cells to relatively high physiological shear stress has antiproliferative and vasoprotective effects. The present study hypothesizes that EECP inhibits intimal hyperplasia and atherogenesis by modifying shear stress-responsive gene expression. Methods and Results-Thirty-five male pigs were randomly assigned to 3 groups: high-cholesterol diet (nϭ11), high-cholesterol diet plus EECP (nϭ17), and usual diet (control; nϭ7). The coronary arteries and aortas were collected for histopathological study and immunohistochemical and Western blot analysis. The peak diastolic arterial wall shear stress during EECP increased significantly compared with before EECP (49.62Ϯ10.71 versus 23.92Ϯ7.28 dyne/cm 2 ; PϽ0.001). Intimal hyperplasia was observed in the coronary arteries of the high-cholesterol diet group, whereas in animals receiving EECP, the intima-to-media area ratio was significantly decreased by 41.59% (21.27Ϯ10.00% versus 36.41Ϯ16.69%; Pϭ0.008). Hypercholesterolemia attenuated the protein expression of endothelial NO synthase and enhanced the phosphorylation of extracellular signal-regulated kinases 1/2. EECP treatment alleviated these adverse changes. Conclusions-EECP reduces hypercholesterolemia-induced endothelial damage, arrests vascular smooth muscle cell proliferation and migration, decreases proliferating cell nuclear antigen proliferative index, suppresses extracellular matrix formation, and eventually inhibits intimal hyperplasia and the development of atherosclerosis by increasing the arterial wall shear stress, which in turn activates the endothelial NO synthase/NO pathway and probably suppresses extracellular signal-regulated kinases 1/2 overactivation. (Circulation. 2007;116:526-534.)

An ideal gene carrier is required both in safety and efficiency for transfection. Polyethylenimine (PEI), a well-studied cationic polymer, has been proved with high transfection efficiency, but is reported as toxicity in many cell lines. In this study, PEI was coupled with polyethylene glycol (PEG) to reduce its cytotoxicity. PEG-PEI copolymers were synthesized with isoporon diisocyanate (IPDI) in two steps. A set of PEG-PEI with different PEG molecular weights (MWs) and amounts of PEG were synthesized. The molecular structure of the resulting copolymers was evaluated by nuclear magnetic resonance spectroscopy ((1)H NMR), infrared spectroscopy (IR), and gel permeation chromatography (GPC), all of which had successfully verified formation of the copolymers. The particle size and zeta potential of polymer/DNA complexes were measured, and their cytotoxicity and transfection efficiency in Hela cells were evaluated. We found that the copolymer block structure significantly influenced not only the physicochemical properties of complexes, but also their cytotoxicity and transfection efficiency. PEG (5 kDa) significantly reduced the diameter of the spherical complexes. The zeta potential of complexes was reduced with increasing amount of PEG grafting. Cytotoxicity was dependent not on PEG MW but on the amount of PEG grafting. Copolymer PEG-PEI (2-25-1) with 1.89 PEG (2 kDa) was proved to be more efficient for in vitro gene transfer. In conclusion, PEG MW and the degree of PEGylation were found to significantly influence the biological activity of PEG-PEI/DNA complexes. These results provide new sights into the studies using block copolymer as gene delivery systems.

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We report the synthesis and characterization of a polysaccharide crosslinker of tetraaniline grafting oxidized sodium alginate with large aldehyde and carboxylic groups. We demonstrate that this copolymer has the following properties: it is water soluble under any pH, biodegradable, electroactive, and noncytotoxic; it can self-assemble into nanoparticles with large active functional groups on the outer surface; it can crosslink materials with amino and aminoderivative groups like gelatin to form hydrogels, and thus the electroactivity is readily introduced to the materials. This copolymer has potential applications in biomedical fields such as tissue engineering, drug delivery, and nerve probes where electroactivity is required.

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Laham RJ. Exercise-induced expression of VEGF and salvation of myocardium in the early stage of myocardial infarction. Am J Physiol Heart Circ Physiol 296: H389 -H395, 2009. First published December 5, 2008; doi:10.1152/ajpheart.01393.2007.-The mechanism of exercise-induced benefit and angiogenesis in ischemic heart disease remains poorly defined. This study was designed to investigate the effects of exercise training on the expression of angiogenic factors and angiogenesis in the infarcted myocardium [myocarial infaction (MI)]. Sixty-three male FVB mice were used for study and were divided into subgroups to test the response to exercise: the time-dependent expression of angiogenic factors to exercise training in normal (group 1; n ϭ 12) and infarcted myocardium (group 2; n ϭ 15) and the exerciseinduced angiogenic response in normal and infarcted myocardium (group 3; n ϭ 20) as well as the impact of exercise preconditioning on infarcted myocardium (group 4; n ϭ 26). Exercise training consisted of daily treadmill exercise for 1 h for 3 days. Expression of VEGF and its receptors Flt-1 and Flk-1 was upregulated by exercise training in mice with MI. Exercise-induced VEGF expression in the MI group was higher than that in the sham (control) group. Cell proliferation assessment showed a significantly higher (P Ͻ 0.05) number of bromodeoxyuridine-positive cells in post-MI mice in the exercise group as opposed to post-MI mice in the sedentary group. 2,3,5-Triphenyltetrazolium chloride staining revealed a profound difference in the size of MI (18.25 Ϯ 2.93%) in the exercise group versus the sedentary group (29.26 Ϯ 7.64%, P ϭ 0.02). Moreover, exercise preconditioning before MI promoted VEGF expression at both mRNA and protein levels. In conclusion, activation of VEGF and its receptors occurs in the infarcted mice heart in response to exercise, which results in decreased infarct size and improved angiogenesis.exercise; angiogenesis; ischemic heart disease; vascular endothelial growth factor EXERCISE AND PHYSICAL ACTIVITY are known to prevent the development of coronary artery disease and reduce symptoms in patients with established cardiovascular disease (26). In fact, a meta-analysis of 48 randomized trials of cardiac rehabilitation showed that, compared with the usual care, cardiac rehabilitation reduced total mortality by 20% and cardiac mortality by 26% (25). The precise mechanisms by which exercise therapy improves mortality in patients with coronary heart disease has not been fully elucidated (16,26). Exercise training has been shown to have beneficial effects on the coronary vasculature, including myocardial oxygen demand, endothelial function, autonomic tone, inflammatory markers, and the development of coronary collateral vessels (5, 28). However, the direct effect of exercise on myocardial angiogenesis in ischemic heart disease remains poorly defined.Angiogenesis is the process of formation of new blood vessels, which is mediated by angiogenic factors such as VEGF. Extensive studies have demonstrated that angiog...

Enhanced external counterpulsation (EECP) is a non‐invasive assisted circulation technique and a rich pool of evidence has accumulated for its clinical application in the prevention and management of multiple comorbidities in the elderly population, including angina, heart failure, ischemic cerebrovascular diseases, neurodegenerative diseases, sleep disorder, diabetes and its complications, ischemic eye diseases, sudden hearing loss and erectile dysfunction, as well as various psychological and psychiatric conditions. When applying EECP to elderly patients, emphasis should be placed on issues such as safety assessment, risk management and protocol individualization, as well as the monitoring of efficacy during and after treatment.