Dataset Information

Identification of Differential Roles of MicroRNA-33a and -33b During Atherosclerosis Progression With Genetically Modified Mice.

ABSTRACT: Background Micro RNA (miR)-33 targets cholesterol transporter ATP -binding cassette protein A1 and other antiatherogenic targets and contributes to atherogenic progression. Its inhibition or deletion is known to result in the amelioration of atherosclerosis in mice. However, mice lack the other member of the miR-33 family, miR-33b, which exists in humans and other large mammals. Thus, precise evaluation and comparison of the responsibilities of these 2 miRs during the progression of atherosclerosis has not been reported, although they are essential. Methods and Results In this study, we performed a comprehensive analysis of the difference between the function of miR-33a and miR-33b using genetically modified mice. We generated 4 strains with or without miR-33a and miR-33b. Comparison between mice with only miR-33a (wild-type mice) and mice with only miR-33b (miR-33a^-/-/miR-33b^+/+) revealed the dominant expression of miR-33b in the liver. To evaluate the whole body atherogenic potency of miR-33a and miR-33b, we developed apolipoprotein E-deficient/miR-33a^+/+/miR-33b^-/- mice and apolipoprotein E-deficient/miR-33a^-/-/miR-33b^+/+ mice. With a high-fat and high-cholesterol diet, the apolipoprotein E-deficient/miR-33a^-/-/miR-33b^+/+ mice developed increased atherosclerotic plaque versus apolipoprotein E-deficient/miR-33a^+/+/miR-33b^-/- mice, in line with the predominant expression of miR-33b in the liver and worsened serum cholesterol profile. By contrast, a bone marrow transplantation study showed no significant difference, which was consistent with the relevant expression levels of miR-33a and miR-33b in bone marrow cells. Conclusions The miR-33 family exhibits differences in distribution and regulation and particularly in the progression of atherosclerosis; miR-33b would be more potent than miR-33a.

SUBMITTER: Koyama S

PROVIDER: S-EPMC6662357 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Identification of Differential Roles of MicroRNA-33a and -33b During Atherosclerosis Progression With Genetically Modified Mice.

Koyama Satoshi S Horie Takahiro T Nishino Tomohiro T Baba Osamu O Sowa Naoya N Miyasaka Yui Y Kuwabara Yasuhide Y Nakao Tetsushi T Nishiga Masataka M Nishi Hitoo H Nakashima Yasuhiro Y Nakazeki Fumiko F Ide Yuya Y Kimura Masahiro M Tsuji Shuhei S Ruiz Rodriguez Randolph R Xu Sijia S Yamasaki Tomohiro T Otani Chiharu C Watanabe Toshimitsu T Nakamura Tomoyuki T Hasegawa Koji K Kimura Takeshi T Ono Koh K

Journal of the American Heart Association 20190627 13

Background Micro RNA (miR)-33 targets cholesterol transporter ATP -binding cassette protein A1 and other antiatherogenic targets and contributes to atherogenic progression. Its inhibition or deletion is known to result in the amelioration of atherosclerosis in mice. However, mice lack the other member of the miR-33 family, miR-33b, which exists in humans and other large mammals. Thus, precise evaluation and comparison of the responsibilities of these 2 miRs during the progression of atherosclero ...[more]

PMID: 31242815

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Project description:BackgroundDistal femur fractures are complex injuries with a high rate of fracture healing problems. Since the widespread of computed tomographic imaging in the diagnosis of distal femur fractures, many fracture characteristics have been discovered. This study aimed to depict the location and frequency of distal femur fracture lines and further analyze the morphological characteristics using the 3-dimensional computed tomography (CT) mapping technique, thus providing more information to solve this challenging clinical problem.MethodsIn total, 217 distal femur fractures in 216 patients were retrospectively reviewed. Fracture fragments on CT were digitally reconstructed and virtually reduced to match a template model. The contour of every fracture fragment was then marked with smooth curves, and the overlap of all fracture lines allowed for the creation of 3-dimensional fracture maps and heat maps. Fracture characteristics were summarized based on these maps.ResultsThis study included 114 left knee injuries, 101 right knee injuries, and 1 case with bilateral injury. Distal femur fractures were most likely to occur among patients aged 61 to 70 years. On the heat map of all 217 fractures, fracture line hot zones were mainly concentrated around the metaphysis, the lateral part of the intercondylar notch, and the patellofemoral joint. Distal femur fractures with three Arbeitsgemeinschaft für Osteosynthesefragen Foundation/Orthopaedic Trauma Association (AO/OTA) types demonstrated distinct fracture characteristics. In total, there were 58 coronal plane fractures (41.1%) in 141 intercondylar fractures.ConclusionsThe intercondylar fracture patterns in AO/OTA type B and type C fractures were similar, while the supracondylar characteristics in AO/OTA type A and type C were different. The findings in this study can help orthopaedic surgeons better understand the fracture morphology on the basis of AO/OTA classification. Further studies are needed to establish a standard biomechanical fracture model and new fixation strategy for better clinical outcomes.

Dataset Information

Identification of Differential Roles of MicroRNA-33a and -33b During Atherosclerosis Progression With Genetically Modified Mice.

Publications

Identification of Differential Roles of MicroRNA-33a and -33b During Atherosclerosis Progression With Genetically Modified Mice.

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