Angiotensin‐(1–7) upregulates expression of adenosine triphosphate‐binding cassette transporter A1 and adenosine triphosphate‐binding cassette transporter G1 through the Mas receptor through the liver X receptor alpha signalling pathway in THP‐1 macrophages treated with angiotensin‐II

Adenosine triphosphate‐binding cassette transporter A1 (ABCA1) and ABCG1 play crucial roles in reverse cholesterol transport, and have anti‐atherosclerosis effects, and liver X receptor alpha (LXRα) can stimulate cholesterol efflux through these transporters. Angiotensin (Ang)‐(1–7) can protect endothelial cells, inhibit smooth muscle cell growth, ameliorate inflammation and exert anti‐atherosclerotic effects. In the present study, we attempted to clarify the effect of Ang‐(1–7) on expression of ABCA1 and ABCG1, and explored the role of LXRα in the regulation of ABCA1 and ABCG1 in THP‐1 macrophages that had been incubated with angiotensin‐II (AngII). Ang‐(1–7) increased ABCA1 and ABCG1 expression in a concentration‐dependent manner at both the mRNA and protein levels, promoted cholesterol efflux, and decreased cholesterol content in THP‐1 macrophages treated with AngII. Furthermore, Ang‐(1–7) upregulated the expression of LXRα in a concentration‐dependent manner in these cells. LXRα small interfering RNA, as well as the Mas receptor antagonist A‐779, completely abolished these effects of Ang‐(1–7). In summary, Ang‐(1–7) upregulates ABCA1 and ABCG1 expression in THP‐1 macrophages treated with AngII through the Mas receptor, via the LXRα pathway. This novel insight into the molecular mechanism underlying Ang‐(1–7) and AngII interaction could prove useful for developing new strategies for treatment of cardiovascular diseases.     

高血压患者红细胞ATP含量、红细胞膜ATP酶活性与钙、镁代谢的研究

目的:探讨原发性高血压(EH)患者红细胞ATP含量,红细胞膜Na~ ,K~ -ATP酶和Ca~(2 ),Mg~(2 )-ATP酶的活性与红细胞内钙、镁含量之间的关系及意义。方法:观察EH患者和正常对照红细胞内ca~(2 ),Mg~(2 )水平,红细胞内ATP含量,红细胞膜Na~ ,K~ -ATP酶和Ca~(2 ),Mg~(2 )-ATP酶的活性变化。结果:原发性高血压患者与正常对照相比,红细胞膜Na~ ,K~ -ATP酶、Ca~(2 ),Mg~(2 )-ATP酶活性和红细胞内Mg~(2 )含量减低,红细胞内Ca~(2 )含量升高,(P均<0.05)。红细胞内ATP含量在原发性高血压患者和正常对照之间无显著性差别。原发性高血压患者中,平均动脉压与Na~ ,K~ -ATP酶和Ca~(2 ),Mg~(2 )-ATP酶活性负相关(P<0.01),与红细胞内钙正相关(P<0.01);Ca2~(2 ),Mg~(2 )-ATP酶的活性与红细胞内Ca~(2 )含量负相关(P<0.01);红细胞内ATP含量与红细胞内镁含量正相关(P<0.05),与红细胞膜Na~ ,K~ -ATP酶、ca~(2 ),Mg~(2 )-ATP酶活性之间无统计学联系。结论:高血压的发生与细胞膜离子的主动转运失常而致细胞内Ca~(2 )水平升高密切相关,而细胞内Mg~(2 )含量与细胞糖代谢有关。     

Using positron emission tomography to study human ketone body metabolism: A review

Ketone bodies – 3-hydroxybutyrate and acetoacetate – are important fuel substrates, which can be oxidized by most tissues in the body. They are synthesized in the liver and are derived from fatty acids released from adipose tissue. Intriguingly, under conditions of stress such as fasting, arterio-venous catheterization studies have shown that the brain switches from the use of almost 100% glucose to the use of > 50–60% ketone bodies. A similar adaptive mechanism is observed in the heart, where fasting induces a shift toward ketone body uptake that provides the myocardium with an alternate fuel source and also favorably affects myocardial contractility. Within the past years there has been a renewed interest in ketone bodies and the possible beneficial effects of fasting/semi-fasting/exercising and other “ketogenic” regimens have received much attention. In this perspective, it is promising that positron emission tomography (PET) techniques with isotopically labeled ketone bodies, fatty acids and glucose offer an opportunity to study interactions between ketone body, fatty acid and glucose metabolism in tissues such as the brain and heart. PET scans are non-invasive and thus eliminates the need to place catheters in vascular territories not easily accessible. The short half-life of e.g. 11C-labeled PET tracers even allows multiple scans on the same study day and reduces the total radiation burden associated with the procedure. This short review aims to give an overview of current knowledge on ketone body metabolism obtained by PET studies and discusses the methodological challenges and perspectives involved in PET ketone body research.     

SIRT3 regulation of mitochondrial oxidative stress

Mitochondria play a central role in the production of reactive oxygen species as byproducts of metabolism and energy production. In order to protect cellular structures from oxidative stress-induced damage, cells have evolved elegant mechanisms for mitochondrial ROS detoxification. The mitochondrial sirtuin, SIRT3, is emerging as a pivotal regulator of oxidative stress by deacetylation of substrates involved in both ROS production and detoxification. This review will summarize recent findings on the regulation of mitochondrial ROS homeostasis by SIRT3.