Xinhua Yin

The first-generation drug-eluting stents and coronary endothelial dysfunction.

Recently, a growing body of clinical data has shown that the first generation of drug-eluting stents (1st-gen DES) implantation could elicit coronary conduit artery vasomotor dysfunction at nonstented reference segments as late as 12 months after implantation compared with that seen with bare-metal stents. The mechanism of this phenomenon is still not fully understood. Pathological studies have implicated delayed arterial healing and poor re-endothelialization after the 1st-gen DES implantation. Given the vast use of DES globally, a thorough understanding of the early and long-term safety of these devices is paramount. Therefore, this article systematically reviews the current clinical, pathophysiological, and histopathological available data regarding 1st-gen DES-associated vascular endothelial dysfunction. Meanwhile, we will also review the newer generation of DES and emerging endothelial-friendly technology.

Endothelium-Dependent Vasomotor Dysfunction in Pig Coronary Arteries With Paclitaxel-Eluting Stents Is Associated With Inflammation and Oxidative Stress

OBJECTIVES We sought to evaluate coronary epicardial and intramyocardial resistance, arterial vasomotor function, local inflammatory reaction, and superoxide anion (O(2)(.-)) production after overlapping paclitaxel-eluting stent (PES) implantation in a porcine model. BACKGROUND PES implantation has been shown to elicit coronary vasomotor dysfunction. However, underlying mechanisms remain largely unknown. METHODS Nine pigs received overlapping PES and bare-metal stents (BMS) in the coronary arteries, and 3 sham animals were naïve. At 1 month, inflammatory response at the overlapped region was assessed by histopathology and scanning electron microscopy. Endothelial vasomotor function and O(2)(*-) at nonstented coronary reference segments were measured by angiography and organ chamber tensiometry, and lucigenin luminometry; vasomotor function of distal resistance arteries was measured by myography. RESULTS Paclitaxel-eluting stents showed reduced late lumen loss, but inflammation and luminal inflammatory cell adherence were higher than for BMS (p < 0.001) at overlapped segments. Endothelium-dependent relaxation to substance P was significantly impaired in PES at nonstented coronary reference segments (>or=15 mm proximally and distally) and perfusion bed resistance arteries (p < 0.05). In contrast, endothelium-independent relaxation to nitroglycerin and sodium-nitroprusside was similar between groups. Local O(2)(*-) production at both proximal and distal nonstented coronary reference segments was elevated for PES when compared with O(2)(*-) production in BMS and naïve arteries (p < 0.001). CONCLUSIONS Abnormal endothelium-dependent relaxation at both coronary conduit and resistance arteries was demonstrated after overlapping PES implantation. Profound localized inflammatory reaction, as well as enhanced local oxidative stress, may contribute to vasomotor dysfunction.

Ghrelin and cardiovascular diseases.

Ghrelin, a newly discovered bioactive peptide, is a natural endogenous ligand of the growth hormone (GH) secretagogue receptor and initially identified as a strong stimulant for the release of GH. Subsequent research has shown that ghrelin and its various receptors are ubiquitous in many other organs and tissues. Moreover, they participate in the regulation of appetite, energy, bodyweight, metabolism of glucose and fat, as well as modulation of gastrointestinal, cardiovascular, pulmonary, immune functions and cell proliferation/apoptosis. Increasing evidence has demonstrated that ghrelin has a close relationship with cardiovascular system. Ghrelin and its receptors are widely distributed in cardiovascular tissues, and there is no doubt that the effects of ghrelin in the cardiovascular system are mediated not only via its growth-hormone-releasing effect but also by its direct effects on the heart. Exogenous administration of ghrelin can dilate peripheral blood vessels, constrict coronary artery, improve endothelial function, as well as inhibit myocardial cell apoptosis. So, ghrelin may have cardiovascular protective effect, including lowering of blood pressure, regulation of atherosclerosis, and protection from ischemia/reperfusion injury as well as improving the prognosis of myocardial infarction and heart failure. Some of these new functions of ghrelin may provide new potential therapeutic opportunities for ghrelin in cardiovascular medicine. In this paper, we will review the existing evidence for cardiovascular effects of ghrelin, including the cardiovascular function, the variations in ghrelin plasma levels in pathophysiologicalogical conditions, the possible protective mechanisms of ghrelin, as well as its future potential therapeutic roles.

Polymer-free cerivastatin-eluting stent shows superior neointimal inhibition with preserved vasomotor function compared to polymer-based paclitaxel-eluting stent in rabbit iliac arteries

AIMS The present study was designed to evaluate vasomotor function and vascular biological responses following a novel non-polymeric cerivastatin-eluting stent (CES) versus polymer-based paclitaxel-eluting stent (PES) in a rabbit iliac artery model. Optimisation of DES components and non-polymeric stents may contribute to vascular healing and beneficial to vasomotor function. METHODS AND RESULTS In vitro human aortic and coronary smooth muscle cells (hASMC & hCSMC), as well as endothelial cells (hAEC & hCEC) were cultured. IC50 curves were determined for cerivastatin (CER). In vivo PES (n=6) and CES (n=12) stents were implanted in nine rabbits. Vasomotor function was investigated at 28 days by acetylcholine (ACh) followed by histopathological and histomorphometric analyses. CER was cytotoxic to hASMC and hCSMC (IC50s of 10-6 M and 10-5 M, respectively), although such cytotoxic effects were not observed for hAEC and hCEC at maximal study dose. PES-associated vasodilation response to endothelial-dependent ACh was significantly suppressed at both proximal and distal adjacent arterial segments, as compared to CES. Furthermore, microscopically, neointimal inhibition quantified by the neointimal cross-sectional area (IA) was superior with CES (0.60 + or - 0.27 mm(2)) compared to PES (1.35 + or - 0.16 mm(2); P <0.05). Medial area was smaller for PES (0.3 + or - 0.04 mm(2)) than CES (0.5 + or - 0.03 mm(2), p <0.001). Additionally, significant inflammation and fibrin deposition was clearly evidenced in PES compared to CES (p <0.05). CONCLUSIONS CER elicits a differential effect on hSMC compared to hEC in vitro. In contrast to PES, a novel bioabsorbable sol-gel coated CES demonstrated effective neointimal inhibition with less vessel wall toxicity accompanied by preservation of vasomotor function in the rabbit iliac model.

IMPAIRMENT OF VASOMOTOR FUNCTION OF CONDUIT BUT NOT RESISTANCE ARTERIES AFTER LONG-TERM FEMORAL ARTERY OCCLUSION

Background: Early treatments are profoundly beneicial and improve outcomes in peripheral arterial disease (PAD). However, asymptomatic patients do not receive the optimal treatments as early as patients with CAD. So far, the changes in the vasomotor function with the chronic occlusion of the supericial femoral artery (SFA) are still unknown. We evaluated endothelium function for both conduit and collateral resistance arteries (CA) following long-term SFA ligation in Yucatan miniswine.