Molecular characterization of atherosclerosis in HIV positive persons.
Molecular characterization of atherosclerosis in HIV positive persons.
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HIV阳性者动脉粥样硬化的分子特征
DOI：
10.1038/s41598-021-82429-4
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发表时间：
2021-02-05
影响因子：
4.6
通讯作者：
Thakar J
中科院分区：
文献类型：
--
作者：
Cornwell A;Palli R;Singh MV;Benoodt L;Tyrell A;Abe JI;Schifitto G;Maggirwar SB;Thakar J
艾滋病毒携带者患动脉粥样硬化(AS)的风险更高。这种风险的发病机制尚不完全清楚。[目的]通过对13例HIV感染者和12例匹配的HIV阴性AS患者外周血单个核细胞(PBMC)中细胞因子和趋化因子水平进行测序，以评估其参与的调控网络。已知microRNAs(MiRNAs)在HIV感染中发挥作用，并可能调节基因调控以驱动AS。因此，我们进一步评估了12名患有和不伴有动脉粥样硬化的HIV+ 患者的PBMC中miRNA的表达。我们鉴定了12个在HIV+ AS+ 和HIV+ 之间差异表达的miRNAs，并通过RT-qPCR验证了其中的5个。虽然其中少数miRNAs与艾滋病毒和动脉粥样硬化有关，但其他miRNAs是新的。结合miRNA测量和mRNA，我们确定了27个靶基因，包括关键的钠和碳酸氢盐转运体SLC4A7，它们在动脉粥样硬化过程中可能存在调节异常。此外，我们还发现，血浆细胞因子水平与转录因子活性和PBMC中miRNA的表达有关。例如，BACH2活性与IL-1β、IL-15和MIP-1α有关。IP10和肿瘤坏死因子α水平与miR-12 4-3p显著相关。最后，将所有数据类型整合到一个单一网络中显示，在艾滋病毒+ 组中，miRNA在网络调节中的重要性增加，而在艾滋病毒+ AS+ 组中，细胞因子的重要性增加。
People living with HIV are at higher risk of atherosclerosis (AS). The pathogenesis of this risk is not fully understood. To assess the regulatory networks involved in AS we sequenced mRNA of the peripheral blood mononuclear cells (PBMCs) and measured cytokine and chemokine levels in the plasma of 13 persons living with HIV and 12 matched HIV-negative persons with and without AS. microRNAs (miRNAs) are known to play a role in HIV infection and may modulate gene regulation to drive AS. Hence, we further assessed miRNA expression in PBMCs of a subset of 12 HIV+ people with and without atherosclerosis. We identified 12 miRNAs differentially expressed between HIV+ AS+ and HIV+ , and validated 5 of those by RT-qPCR. While a few of these miRNAs have been implicated in HIV and atherosclerosis, others are novel. Integrating miRNA measurements with mRNA, we identified 27 target genes including SLC4A7, a critical sodium and bicarbonate transporter, that are potentially dysregulated during atherosclerosis. Additionally, we uncovered that levels of plasma cytokines were associated with transcription factor activity and miRNA expression in PBMCs. For example, BACH2 activity was associated with IL-1β, IL-15, and MIP-1α. IP10 and TNFα levels were associated with miR-124-3p. Finally, integration of all data types into a single network revealed increased importance of miRNAs in network regulation of the HIV+ group in contrast with increased importance of cytokines in the HIV+ AS+ group.
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影响因子：
39
作者：
Freiberg MS;Chang CC;Kuller LH;Skanderson M;Lowy E;Kraemer KL;Butt AA;Bidwell Goetz M;Leaf D;Oursler KA;Rimland D;Rodriguez Barradas M;Brown S;Gibert C;McGinnis K;Crothers K;Sico J;Crane H;Warner A;Gottlieb S;Gottdiener J;Tracy RP;Budoff M;Watson C;Armah KA;Doebler D;Bryant K;Justice AC
通讯作者：
Justice AC
影响因子：
3.7
作者：
Baras AS;Mitchell CJ;Myers JR;Gupta S;Weng LC;Ashton JM;Cornish TC;Pandey A;Halushka MK
通讯作者：
Halushka MK
DOI：
10.1097/qad.0b013e32832d3b85
发表时间：
2009-09-10
期刊：
AIDS (London, England)
影响因子：
--
作者：
Grunfeld C;Delaney JA;Wanke C;Currier JS;Scherzer R;Biggs ML;Tien PC;Shlipak MG;Sidney S;Polak JF;O'Leary D;Bacchetti P;Kronmal RA
通讯作者：
Kronmal RA
DOI：
10.1097/qai.0000000000000756
发表时间：
2015-11-01
期刊：
Journal of acquired immune deficiency syndromes (1999)
影响因子：
--
作者：
Hubert A;Subra C;Jenabian MA;Tremblay Labrecque PF;Tremblay C;Laffont B;Provost P;Routy JP;Gilbert C
通讯作者：
Gilbert C
影响因子：
37.8
作者：
Boedtkjer, Ebbe;Praetorius, Jeppe;Aalkjaer, Christian
通讯作者：
Aalkjaer, Christian