Overexpression of TFAM or Twinkle Increases mtDNA Copy Number and Facilitates Cardioprotection Associated with Limited Mitochondrial Oxidative Stress

Background Mitochondrial DNA (mtDNA) copy number decreases in animal and human heart failure (HF), yet its role in cardiomyocytes remains to be elucidated. Thus, we investigated the cardioprotective function of increased mtDNA copy number resulting from the overexpression of human transcription factor A of mitochondria (TFAM) or Twinkle helicase in volume overload (VO)-induced HF. Methods and Results Two strains of transgenic (TG) mice, one overexpressing TFAM and the other overexpressing Twinkle helicase, exhibit an approximately 2-fold equivalent increase in mtDNA copy number in heart. These TG mice display similar attenuations in eccentric hypertrophy and improved cardiac function compared to wild-type (WT) mice without any deterioration of mitochondrial enzymatic activities in response to VO, which was accompanied by a reduction in matrix-metalloproteinase (MMP) activity and reactive oxygen species after 8 weeks of VO. Moreover, acute VO-induced MMP-2 and MMP-9 upregulation was also suppressed at 24 h in both TG mice. In isolated rat cardiomyocytes, mitochondrial reactive oxygen species (mitoROS) upregulated MMP-2 and MMP-9 expression, and human TFAM (hTFAM) overexpression suppressed mitoROS and their upregulation. Additionally, mitoROS were equally suppressed in H9c2 rat cardiomyoblasts that overexpress hTFAM or rat Twinkle, both of which exhibit increased mtDNA copy number. Furthermore, mitoROS and mitochondrial protein oxidation from both TG mice were suppressed compared to WT mice. Conclusions The overexpression of TFAM or Twinkle results in increased mtDNA copy number and facilitates cardioprotection associated with limited mitochondrial oxidative stress. Our findings suggest that increasing mtDNA copy number could be a useful therapeutic strategy to target mitoROS in HF.Peer reviewe

Persistent high fever and systemic inflammation induced by percutaneous coronary intervention-related periaortitis

Takamori Kakino, Tomohiro Nakayama, Hideo YamamotoDepartment of Cardiology and Radiology, Kyushu Kosei–Nenkin Hospital, Kitakyushi City, JapanAbstract: After coronary catheterization, fever sometimes occurs, usually transiently. We report a very rare case that suggests persistent high fever and systemic inflammation might be caused by periaortitis induced by coronary catheterization including percutaneous coronary intervention.Keywords: periaortitis, percutaneous coronary intervention, fever, computed tomograph

Risk factors for coronary artery calcification in Japanese patients

AbstractBackgroundBecause the prevalence of coronary artery calcification is lower among Japanese than among Western individuals, aspects of the Japanese lifestyle might be related to the development of calcification. We aimed to clarify the relationship between coronary artery calcium scores in Japanese patients and various lifestyle factors among the Japanese population.MethodsStudy subjects were patients aged ≥20 years who underwent multidetector-row computed tomography. A total of 201 patients agreed to take part in this study and answered a questionnaire regarding lifestyle, medical history, and other factors.ResultsOld age, current and former smoking, sedentary work, short sleep time, coronary artery stenosis, treatment with statins, medical history of cerebrovascular disease, medical history of angina pectoris, medical history of ischemic heart disease, and medical history of dyslipidemia were associated with higher odds ratios than the other factors examined, while the Japanese-style breakfast (e.g. boiled rice, miso soup, grilled fish) was associated with lower odds ratios.ConclusionsIn this study, smoking, sedentary work, short sleep time, and the Japanese-style breakfast were lifestyle factors related to coronary artery calcification. The lifestyle of Japanese people may be related to coronary calcification

Representative pressure-volume loops at 3 levels of left ventricular assist device (LVAD) support in a normal dog.

<p>The solid line represents pressure-volume (PV) loop with no LVAD support (Control). Partial LVAD support (p-LVAD) decreases left ventricle (LV) end-diastolic volume and increases mean arterial pressure (AP), thus PVA does not decrease much (dotted line). On the other hand, total LVAD support (t-LVAD) lowers LV pressure to below AP and markedly reduces PVA (double line).</p

Impact of level of left ventricular assist device (LVAD) support on hemodynamics in normal dogs.

<p>Impact of level of left ventricular assist device (LVAD) support on hemodynamics in normal dogs.</p