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Soon after AMI, Japanese patients exhibited a 3-fold-greater incidence of spasm and greater vasoconstriction of nonspastic segments after acetylcholine than Caucasians. The causes of such differences warrant further investigation because they may have relevant pathophysiological and therapeutic implications.

Nitric oxide accounts for the activity of endothelium-derived relaxing factor, which seems to have an important role in vasodilation and inhibition of platelet aggregation. In endothelial cells, one isoform of nitric-oxide synthase is constitutively expressed. Analysis of the cDNA encoding the human endothelial nitric-oxide synthase revealed that the mRNA is 4.1 kb in size and that the translated protein consists of 1203 amino acids. We have cloned a genomic DNA encoding the human endothelial nitric-oxide synthase and analyzed the entire nucleotide sequence of the gene. The gene consists of 26 exons with a total size of 21 kb. The 5' flanking region of the gene lacks TATA boxes, but it contains putative Spl-binding sites in (G+C)-rich regions. Of particular interest is the fact that a shear-stress-responsive element is located at position -985, which probably regulates the nitric-oxide-synthase gene in response to fluid mechanical forces at the transcriptional level in the vascular endothelium. Two minisatellite sequences are detectable in introns 2 and 8; a 32-bp consensus sequence repeats 38 times and a 57-bp consensus sequence repeats ten times. We found polymorphisms of the BarnHI fragment containing the former minisatellite sequence in genomic DNA from pedigree family members. Furthermore, five tandem repeats of a 27-bp core consensus sequence and 35 repeats of a dinucleotide (CA) are located in introns 4 and 13, respectively. These repeat sequences will probably provide genetic markers for gene mapping and linkage analysis of inherited diseases including cardiovascular diseases.Nitric oxide has been recently implicated in a number of diverse physiological processes, including smooth muscle relaxation, inhibition of platelet aggregation, neurotransmission, immune regulation and penile erection 11, 21. Nitric oxide is produced from L-arginine by nitric-oxide synthase with a concomitant production of L-citrulline. There appears to be at least three distinct isoforms of nitric-oxide synthase [l-41. All three isoforms contain consensus sequences for the binding of FMN, FAD, and NADPH cofactors, and the structures of the isoforms have close homology to cytochrome P-450 reductase 11, 2, 51.Endothelium-derived relaxing factor 161 is important in the regulation of vasomotor tone and blood flow by inhibiting smooth muscle contraction and platelet aggregation [7]. Recently, several groups reported that nitric oxide accountsCorrespondence to

Long-term safety and efficacy of drug-eluting stents remains controversial. The CREDO-Kyoto registry cohort-2 is a physician-initiated non-company sponsored multi-center registry enrolling consecutive patients undergoing first coronary revascularization in 26 centers in Japan. We compared 3-year outcome between patients treated with sirolimus-eluting stent (SES) only (5092 patients) and bare-metal stent (BMS) only (5405 patients). SES-use as compared with BMS-use was associated with significantly lower adjusted risk for all-cause death [hazard ratio (HR) [95% confidence interval (CI)] 0.72 (0.59-0.87), P = 0.0007], which was mainly driven by the reduction in non-cardiac death [HR (95% CI) 0.64 (0.48-0.85), P = 0.002]. The risk of cardiac death [HR (95% CI) 0.82 (0.63-1.07), P = 0.15], myocardial infarction [HR (95% CI) 0.73 (0.51-1.03), P = 0.07] and definite stent thrombosis [HR (95% CI) 0.62 (0.35-1.09), P = 0.1] was not different between the two groups. Despite longer duration of thienopyridine administration, SES-use was associated with significantly lower risk for bleeding [HR (95% CI) 0.75 (0.6-0.95), P = 0.02] and similar risk for stroke [HR (95% CI) 1.0 (0.75-1.34), P = 1.0]. The risk for target-lesion revascularization (TLR) was markedly lower in the SES group [HR (95% CI) 0.42 (0.36-0.48), P < 0.0001]. The direction and magnitude of the effect of SES relative to BMS in patients presenting acute myocardial infarction (AMI) were similar to those in patients presenting otherwise. In conclusion, SES-use as compared with BMS-use was associated with marked reduction of TLR without any increases in death, myocardial infarction, stent thrombosis, stroke and bleeding in real world clinical practice regardless of clinical presentation including AMI.

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