- 著者
- Yuji Mizuno Seiji Hokimoto Eisaku Harada Kenji Kinoshita Michihiro Yoshimura Hirofumi Yasue
- 出版者
- The Japanese Circulation Society
- 雑誌
- Circulation Journal (ISSN:13469843)
- 巻号頁・発行日
- pp.CJ-16-0969, (Released:2016-11-29)
- 参考文献数
- 36
- 被引用文献数
- 16 22
Background:Coronary spastic angina (CSA) is common among East Asians and tobacco smoking (TS) is an established risk factor for CSA. Aldehyde dehydrogenase 2 (ALDH2) plays a key role in removing reactive toxic aldehydes and a deficient variant ALDH2 genotype (ALDH2*2) is prevalent among East Asians. We examined the interaction between TS andALDH2*2as a risk factor for CSA to better understand the disease pathogenesis.Methods and Results:The study subjects comprised 410 patients (258 men, 152 women; mean age, 66.3±11.5) in whom intracoronary injection of acetylcholine was performed on suspicion of CSA.ALDH2genotyping was performed by direct application of the Taqman polymerase chain reaction system. Of the study subjects, 244 had CSA proven and 166 were non-CSA. The frequencies of male sex,ALDH2*2, alcohol flushing syndrome, TS, coronary organic stenosis, and plasma levels of uric acid were higher (P<0.001, P<0.001, P<0.001, P<0.001, P<0.001, and P=0.015, respectively) and that of high-density lipoprotein cholesterol lower (P=0.002) in the CSA than non-CSA group. Multivariable logistic regression analysis revealed thatALDH2*2and TS were significant risk factors for CSA (P<0.001 and P=0.002, respectively).ALDH2*2exacerbated TS risk for CSA more than the multiplicative effects of each.Conclusions:ALDH2*2synergistically exacerbates TS risk for CSA, probably through aldehydes.
- 著者
- Yuji Mizuno Eisaku Harada Daisuke Katoh Yusuke Kashiwagi Yoshinobu Morikawa Hitoshi Nakagawa Michihiro Yoshimura Yoshihiko Saito Hirofumi Yasue
- 出版者
- The Japan Endocrine Society
- 雑誌
- Endocrine Journal (ISSN:09188959)
- 巻号頁・発行日
- vol.60, no.1, pp.87-95, 2013 (Released:2013-01-31)
- 参考文献数
- 46
- 被引用文献数
- 16 27
B-type natriuretic peptide (BNP) is produced by the heart and its plasma level is increased with the severity of left ventricular (LV) dysfunction/hypertrophy. The normal heart preferentially utilizes fatty acids as energy substrates. Plasma BNP levels are reported to be lower in obese individuals. We examined the relationship between BNP production and plasma free fatty acids (FFA), homeostasis model assessment of insulin resistance (HOMA-IR), and LV dysfunction/ hypertrophy. We examined the plasma BNP levels and FFA at the aortic root (AO) and coronary sinus (CS) as well as hemodynamic parameters in 62 patients (38 men and 24 women, 62.5±11.7 yrs) who underwent cardiac catheterization. Log BNP (AO) had a significant positive correlation with log BNP (CS-AO) (r=0.877, PPPPPPP=0.001). The multivariable regression analyses including log HOMA-IR, LVMI, and age as an independent variable revealed that HOMA-IR and LVMI were significant predictors of log BNP (CS-AO) or BNP production (P=0.001 and 0.004, respectively). We conclude that plasma BNP levels are determined primarily by cardiac production and that insulin resistance is a significant predictor of cardiac BNP production independent of LV hypertrophy in obese individuals.
- 著者
- Hirofumi YASUE Yuji MIZUNO Eisaku HARADA
- 出版者
- The Japan Academy
- 雑誌
- Proceedings of the Japan Academy, Series B (ISSN:03862208)
- 巻号頁・発行日
- vol.95, no.2, pp.53-66, 2019-02-08 (Released:2019-02-08)
- 参考文献数
- 110
- 被引用文献数
- 32 76
Coronary artery spasm (CAS) plays an important role in the pathogenesis of ischemic heart disease, including angina pectoris, myocardial infarction, and sudden death, occurring most often from midnight to early morning. CAS is prevalent among East Asians and is associated with an aldehyde dehydrogenase 2 (ALDH2)-deficient genotype (ALDH2*2) and alcohol flushing, which is prevalent among East Asians but is virtually non-existent in other populations. ALDH2 eliminates not only acetaldehyde but also other toxic aldehydes from lipid peroxidation and tobacco smoking, thereby protecting tissues and cells from oxidative damage. Risk factors for CAS include smoking and genetic polymorphisms including those of ALDH2*2, endothelial NO synthase, paraoxonase I, and interleukin-6. Accordingly, oxidative stress, endothelial dysfunction, and low-grade chronic inflammation play an important role in the pathogenesis of CAS, leading to increased coronary smooth muscle Ca2+ sensitivity through RhoA/ROCK activation and resultant hypercontraction. Ca-channel blockers blocking the intracellular entry of Ca2+ are specifically effective for treatment for CAS.