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Author Aiqin Cao

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Monocyte released HERV-K dUTPase engages TLR4 and MCAM causing endothelial mesenchymal transition.

Shoichiro Otsuki, Toshie Saito, Shalina Taylor, Dan Li, Jan-Renier Moonen, David P Marciano, Rebecca L Harper, Aiqin Cao, Lingli Wang, Maria E Ariza, Marlene Rabinovitch,

Previously we reported heightened expression of human endogenous retroviral protein HERV-K deoxyuridine triphosphate nucleotidohydrolase (dUTPase) in circulating monocytes and pulmonary arterial (PA) adventitial macrophages of PA hypertension (PAH) patients. Furthermore, recombinant HERV-K dUTPase increased IL6 in PA endothelial cells (PAECs) and caused pulmonary hypertension in rats. Here we show that ... Read more >>

JCI Insight (JCI insight)
[2021, :]

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PPARγ-p53-Mediated Vasculoregenerative Program to Reverse Pulmonary Hypertension.

Jan K Hennigs, Aiqin Cao, Caiyun G Li, Minyi Shi, Julia Mienert, Kazuya Miyagawa, Jakob Körbelin, David P Marciano, Pin-I Chen, Matthew Roughley, Matthew V Elliott, Rebecca L Harper, Matthew A Bill, James Chappell, Jan-Renier Moonen, Isabel Diebold, Lingli Wang, Michael P Snyder, Marlene Rabinovitch,

<h4>Rationale</h4>In pulmonary arterial hypertension (PAH), endothelial dysfunction and obliterative vascular disease are associated with DNA damage and impaired signaling of BMPR2 (bone morphogenetic protein type 2 receptor) via two downstream transcription factors, PPARγ (peroxisome proliferator-activated receptor gamma), and p53.<h4>Objective</h4>We investigated the vasculoprotective and regenerative potential of a newly identified PPARγ-p53 ... Read more >>

Circ Res (Circulation research)
[2021, 128(3):401-418]

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Endogenous Retroviral Elements Generate Pathologic Neutrophils and Elastase Rich Exosomes in Pulmonary Arterial Hypertension

Shalina Taylor, Kévin Contrepois, Bérénice Benayoun, Lihua Jiang, Sarasa Isobe, Lingli Wang, Stavros Melemenidis, Mehmet Ozen, Shoichiro Otsuki, Tsutomu Shinohara, Andrew Sweatt, Jordan Kaplan, Aiqin Cao, Jan-Renier Moonen, David Marciano, Mingxia Gu, Kazuya Miyagawa, Patricia Del Rosario, Andrew Hsi, Roger Thompson, Maria-Eugenia Ariza, Utkan Demirci, Roham Zamanian, Francois Haddad, Mark Nicolls, Michael Snyder, Marlene Rabinovitch,

<h4>ABSTRACT</h4> Neutrophil elastase (NE) is implicated in pulmonary arterial hypertension (PAH) but the role of neutrophils in the pathogenesis of PAH is unclear. Here we show that neutrophils from PAH vs. control subjects produce and release increased NE associated with enhanced extracellular trap formation. PAH neutrophils are highly adherent and ... Read more >>

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Smooth Muscle Contact Drives Endothelial Regeneration by BMPR2-Notch1-Mediated Metabolic and Epigenetic Changes.

Kazuya Miyagawa, Minyi Shi, Pin-I Chen, Jan K Hennigs, Zhixin Zhao, Mouer Wang, Caiyun G Li, Toshie Saito, Shalina Taylor, Silin Sa, Aiqin Cao, Lingli Wang, Michael P Snyder, Marlene Rabinovitch,

<h4>Rationale</h4>Maintaining endothelial cells (EC) as a monolayer in the vessel wall depends on their metabolic state and gene expression profile, features influenced by contact with neighboring cells such as pericytes and smooth muscle cells (SMC). Failure to regenerate a normal EC monolayer in response to injury can result in occlusive ... Read more >>

Circ Res (Circulation research)
[2019, 124(2):211-224]

Cited: 16 times

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PPARγ Interaction with UBR5/ATMIN Promotes DNA Repair to Maintain Endothelial Homeostasis.

Caiyun G Li, Cathal Mahon, Nathaly M Sweeney, Erik Verschueren, Vivek Kantamani, Dan Li, Jan K Hennigs, David P Marciano, Isabel Diebold, Ossama Abu-Halawa, Matthew Elliott, Silin Sa, Feng Guo, Lingli Wang, Aiqin Cao, Christophe Guignabert, Julie Sollier, Nils P Nickel, Mark Kaschwich, Karlene A Cimprich, Marlene Rabinovitch,

Using proteomic approaches, we uncovered a DNA damage response (DDR) function for peroxisome proliferator activated receptor γ (PPARγ) through its interaction with the DNA damage sensor MRE11-RAD50-NBS1 (MRN) and the E3 ubiquitin ligase UBR5. We show that PPARγ promotes ATM signaling and is essential for UBR5 activity targeting ATM interactor ... Read more >>

Cell Rep (Cell reports)
[2019, 26(5):1333-1343.e7]

Cited: 10 times

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The Phosphate Fast-Responsive Genes PECP1 and PPsPase1 Affect Phosphocholine and Phosphoethanolamine Content.

Mohamed Hanchi, Marie-Christine Thibaud, Bertrand Légeret, Keiko Kuwata, Nathalie Pochon, Fred Beisson, Aiqin Cao, Laura Cuyas, Pascale David, Peter Doerner, Ali Ferjani, Fan Lai, Yonghua Li-Beisson, Jérôme Mutterer, Michel Philibert, Kashchandra G Raghothama, Corinne Rivasseau, David Secco, James Whelan, Laurent Nussaume, Hélène Javot,

Phosphate starvation-mediated induction of the HAD-type phosphatases PPsPase1 (AT1G73010) and PECP1 (AT1G17710) has been reported in Arabidopsis (Arabidopsis thaliana). However, little is known about their in vivo function or impact on plant responses to nutrient deficiency. The preferences of PPsPase1 and PECP1 for different substrates have been studied in vitro ... Read more >>

Plant Physiol (Plant physiology)
[2018, 176(4):2943-2962]

Cited: 4 times

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Codependence of Bone Morphogenetic Protein Receptor 2 and Transforming Growth Factor-β in Elastic Fiber Assembly and Its Perturbation in Pulmonary Arterial Hypertension.

Nancy F Tojais, Aiqin Cao, Ying-Ju Lai, Lingli Wang, Pin-I Chen, Miguel A Alejandre Alcazar, Vinicio A de Jesus Perez, Rachel K Hopper, Christopher J Rhodes, Matthew A Bill, Lynn Y Sakai, Marlene Rabinovitch,

<h4>Objective</h4>We determined in patients with pulmonary arterial (PA) hypertension (PAH) whether in addition to increased production of elastase by PA smooth muscle cells previously reported, PA elastic fibers are susceptible to degradation because of their abnormal assembly.<h4>Approach and results</h4>Fibrillin-1 and elastin are the major components of elastic fibers, and fibrillin-1 ... Read more >>

Arterioscler Thromb Vasc Biol (Arteriosclerosis, thrombosis, and vascular biology)
[2017, 37(8):1559-1569]

Cited: 21 times

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Upregulation of Human Endogenous Retrovirus-K Is Linked to Immunity and Inflammation in Pulmonary Arterial Hypertension.

Toshie Saito, Kazuya Miyagawa, Shih-Yu Chen, Rasa Tamosiuniene, Lingli Wang, Orr Sharpe, Erik Samayoa, Daisuke Harada, Jan-Renier A J Moonen, Aiqin Cao, Pin-I Chen, Jan K Hennigs, Mingxia Gu, Caiyun G Li, Ryan D Leib, Dan Li, Christopher M Adams, Patricia A Del Rosario, Matthew Bill, Francois Haddad, Jose G Montoya, William H Robinson, Wendy J Fantl, Garry P Nolan, Roham T Zamanian, Mark R Nicolls, Charles Y Chiu, Maria E Ariza, Marlene Rabinovitch,

<h4>Background</h4>Immune dysregulation has been linked to occlusive vascular remodeling in pulmonary arterial hypertension (PAH) that is hereditary, idiopathic, or associated with other conditions. Circulating autoantibodies, lung perivascular lymphoid tissue, and elevated cytokines have been related to PAH pathogenesis but without a clear understanding of how these abnormalities are initiated, perpetuated, ... Read more >>

Circulation (Circulation)
[2017, 136(20):1920-1935]

Cited: 16 times

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Patient-Specific iPSC-Derived Endothelial Cells Uncover Pathways that Protect against Pulmonary Hypertension in BMPR2 Mutation Carriers.

Mingxia Gu, Ning-Yi Shao, Silin Sa, Dan Li, Vittavat Termglinchan, Mohamed Ameen, Ioannis Karakikes, Gustavo Sosa, Fabian Grubert, Jaecheol Lee, Aiqin Cao, Shalina Taylor, Yu Ma, Zhixin Zhao, James Chappell, Rizwan Hamid, Eric D Austin, Joseph D Gold, Joseph C Wu, Michael P Snyder, Marlene Rabinovitch,

In familial pulmonary arterial hypertension (FPAH), the autosomal dominant disease-causing BMPR2 mutation is only 20% penetrant, suggesting that genetic variation provides modifiers that alleviate the disease. Here, we used comparison of induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) from three families with unaffected mutation carriers (UMCs), FPAH patients, and gender-matched controls ... Read more >>

Cell Stem Cell (Cell stem cell)
[2017, 20(4):490-504.e5]

Cited: 78 times

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Induced Pluripotent Stem Cell Model of Pulmonary Arterial Hypertension Reveals Novel Gene Expression and Patient Specificity.

Silin Sa, Mingxia Gu, James Chappell, Ning-Yi Shao, Mohamed Ameen, Kathryn A T Elliott, Dan Li, Fabian Grubert, Caiyun G Li, Shalina Taylor, Aiqin Cao, Yu Ma, Ryan Fong, Long Nguyen, Joseph C Wu, Michael P Snyder, Marlene Rabinovitch,

<h4>Rationale</h4>Idiopathic or heritable pulmonary arterial hypertension is characterized by loss and obliteration of lung vasculature. Endothelial cell dysfunction is pivotal to the pathophysiology, but different causal mechanisms may reflect a need for patient-tailored therapies.<h4>Objectives</h4>Endothelial cells differentiated from induced pluripotent stem cells were compared with pulmonary arterial endothelial cells from the ... Read more >>

Am J Respir Crit Care Med (American journal of respiratory and critical care medicine)
[2017, 195(7):930-941]

Cited: 35 times

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Amphetamines promote mitochondrial dysfunction and DNA damage in pulmonary hypertension.

Pin-I Chen, Aiqin Cao, Kazuya Miyagawa, Nancy F Tojais, Jan K Hennigs, Caiyun G Li, Nathaly M Sweeney, Audrey S Inglis, Lingli Wang, Dan Li, Matthew Ye, Brian J Feldman, Marlene Rabinovitch,

Amphetamine (AMPH) or methamphetamine (METH) abuse can cause oxidative damage and is a risk factor for diseases including pulmonary arterial hypertension (PAH). Pulmonary artery endothelial cells (PAECs) from AMPH-associated-PAH patients show DNA damage as judged by γH2AX foci and DNA comet tails. We therefore hypothesized that AMPH induces DNA damage ... Read more >>

JCI Insight (JCI insight)
[2017, 2(2):e90427]

Cited: 25 times

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In Pulmonary Arterial Hypertension, Reduced BMPR2 Promotes Endothelial-to-Mesenchymal Transition via HMGA1 and Its Target Slug.

Rachel K Hopper, Jan-Renier A J Moonen, Isabel Diebold, Aiqin Cao, Christopher J Rhodes, Nancy F Tojais, Jan K Hennigs, Mingxia Gu, Lingli Wang, Marlene Rabinovitch,

<h4>Background</h4>We previously reported high-throughput RNA sequencing analyses that identified heightened expression of the chromatin architectural factor High Mobility Group AT-hook 1 (HMGA1) in pulmonary arterial endothelial cells (PAECs) from patients who had idiopathic pulmonary arterial hypertension (PAH) in comparison with controls. Because HMGA1 promotes epithelial-to-mesenchymal transition in cancer, we hypothesized ... Read more >>

Circulation (Circulation)
[2016, 133(18):1783-1794]

Cited: 86 times

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RNA Sequencing Analysis Detection of a Novel Pathway of Endothelial Dysfunction in Pulmonary Arterial Hypertension.

Christopher J Rhodes, Hogune Im, Aiqin Cao, Jan K Hennigs, Lingli Wang, Silin Sa, Pin-I Chen, Nils P Nickel, Kazuya Miyagawa, Rachel K Hopper, Nancy F Tojais, Caiyun G Li, Mingxia Gu, Edda Spiekerkoetter, Zhaoying Xian, Rui Chen, Mingming Zhao, Mark Kaschwich, Patricia A Del Rosario, Daniel Bernstein, Roham T Zamanian, Joseph C Wu, Michael P Snyder, Marlene Rabinovitch,

RATIONALE:Pulmonary arterial hypertension is characterized by endothelial dysregulation, but global changes in gene expression have not been related to perturbations in function. OBJECTIVES:RNA sequencing was used to discriminate changes in transcriptomes of endothelial cells cultured from lungs of patients with idiopathic pulmonary arterial hypertension versus control subjects and to assess ... Read more >>

Am J Respir Crit Care Med (American journal of respiratory and critical care medicine)
[2015, 192(3):356-366]

Cited: 40 times

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Elafin Reverses Pulmonary Hypertension via Caveolin-1-Dependent Bone Morphogenetic Protein Signaling.

Nils P Nickel, Edda Spiekerkoetter, Mingxia Gu, Caiyun G Li, Hai Li, Mark Kaschwich, Isabel Diebold, Jan K Hennigs, Ki-Yoon Kim, Kazuya Miyagawa, Lingli Wang, Aiqin Cao, Silin Sa, Xinguo Jiang, Raymond W Stockstill, Mark R Nicolls, Roham T Zamanian, Richard D Bland, Marlene Rabinovitch,

<h4>Rationale</h4>Pulmonary arterial hypertension is characterized by endothelial dysfunction, impaired bone morphogenetic protein receptor 2 (BMPR2) signaling, and increased elastase activity. Synthetic elastase inhibitors reverse experimental pulmonary hypertension but cause hepatotoxicity in clinical studies. The endogenous elastase inhibitor elafin attenuates hypoxic pulmonary hypertension in mice, but its potential to improve endothelial ... Read more >>

Am J Respir Crit Care Med (American journal of respiratory and critical care medicine)
[2015, 191(11):1273-1286]

Cited: 67 times

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BMPR2 preserves mitochondrial function and DNA during reoxygenation to promote endothelial cell survival and reverse pulmonary hypertension.

Isabel Diebold, Jan K Hennigs, Kazuya Miyagawa, Caiyun G Li, Nils P Nickel, Mark Kaschwich, Aiqin Cao, Lingli Wang, Sushma Reddy, Pin-I Chen, Kiichi Nakahira, Miguel A Alejandre Alcazar, Rachel K Hopper, Lijuan Ji, Brian J Feldman, Marlene Rabinovitch,

Mitochondrial dysfunction, inflammation, and mutant bone morphogenetic protein receptor 2 (BMPR2) are associated with pulmonary arterial hypertension (PAH), an incurable disease characterized by pulmonary arterial (PA) endothelial cell (EC) apoptosis, decreased microvessels, and occlusive vascular remodeling. We hypothesized that reduced BMPR2 induces PAEC mitochondrial dysfunction, promoting a pro-inflammatory or pro-apoptotic ... Read more >>

Cell Metab (Cell metabolism)
[2015, 21(4):596-608]

Cited: 76 times

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Whole-exome sequencing reveals TopBP1 as a novel gene in idiopathic pulmonary arterial hypertension.

Vinicio A de Jesus Perez, Ke Yuan, Maria A Lyuksyutova, Frederick Dewey, Mark E Orcholski, Eric M Shuffle, Maya Mathur, Luke Yancy, Vanessa Rojas, Caiyun Grace Li, Aiqin Cao, Tero-Pekka Alastalo, Nayer Khazeni, Karlene A Cimprich, Atul J Butte, Euan Ashley, Roham T Zamanian,

<h4>Rationale</h4>Idiopathic pulmonary arterial hypertension (IPAH) is a life-threatening disorder characterized by progressive loss of pulmonary microvessels. Although mutations in the bone morphogenetic receptor 2 (BMPR2) are found in 80% of heritable and ∼15% of patients with IPAH, their low penetrance (∼20%) suggests that other unidentified genetic modifiers are required for ... Read more >>

Am J Respir Crit Care Med (American journal of respiratory and critical care medicine)
[2014, 189(10):1260-1272]

Cited: 42 times

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Reduced BMPR2 expression induces GM-CSF translation and macrophage recruitment in humans and mice to exacerbate pulmonary hypertension.

Hirofumi Sawada, Toshie Saito, Nils P Nickel, Tero-Pekka Alastalo, Jason P Glotzbach, Roshelle Chan, Leila Haghighat, Gabriele Fuchs, Michael Januszyk, Aiqin Cao, Ying-Ju Lai, Vinicio de Jesus Perez, Yu-Mee Kim, Lingli Wang, Pin-I Chen, Edda Spiekerkoetter, Yoshihide Mitani, Geoffrey C Gurtner, Peter Sarnow, Marlene Rabinovitch,

Idiopathic pulmonary arterial hypertension (PAH [IPAH]) is an insidious and potentially fatal disease linked to a mutation or reduced expression of bone morphogenetic protein receptor 2 (BMPR2). Because intravascular inflammatory cells are recruited in IPAH pathogenesis, we hypothesized that reduced BMPR2 enhances production of the potent chemokine granulocyte macrophage colony-stimulating ... Read more >>

J Exp Med (The Journal of experimental medicine)
[2014, 211(2):263-280]

Cited: 65 times

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Reduction of serum free fatty acids and triglycerides by liver-targeted expression of long chain acyl-CoA synthetase 3.

Minhao Wu, Aiqin Cao, Bin Dong, Jingwen Liu,

ACSL3 is a member of the long chain acyl-CoA synthetase (ACSL) family that consists of 5 isozymes responsible for cellular fatty acid metabolism in various tissues in an isozyme-specific manner. Our previous studies have demonstrated that expression of ACSL3 mRNA and protein in liver was specifically increased after feeding hamsters ... Read more >>

Int J Mol Med (International journal of molecular medicine)
[2011, 27(5):655-662]

Cited: 7 times

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Janus kinase activation by cytokine oncostatin M decreases PCSK9 expression in liver cells.

Aiqin Cao, Minhao Wu, Hai Li, Jingwen Liu,

PCSK9 degrades LDL receptor (LDLR) in liver and thereby influences the circulating level of LDL cholesterol. Hence, mechanisms inhibiting PCSK9 expression have potential for cholesterol-lowering intervention. Previously, we demonstrated that oncostatin M (OM) activates LDLR gene transcription, resulting in an increased LDL uptake in HepG2 cells and a reduction of ... Read more >>

J Lipid Res (Journal of lipid research)
[2011, 52(3):518-530]

Cited: 27 times

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Suppression of Idol expression is an additional mechanism underlying statin-induced up-regulation of hepatic LDL receptor expression.

Bin Dong, Minhao Wu, Aiqin Cao, Hai Li, Jingwen Liu,

Recent studies have identified proprotein convertase subtilisin/kexin type 9 (PCSK9) and Idol as negative regulators of low density lipoprotein receptor (LDLR) protein stability. While the induction of PCSK9 transcription has been recognized as a limitation to the statin cholesterol-lowering efficacy at higher doses, it is unknown whether Idol is involved ... Read more >>

Int J Mol Med (International journal of molecular medicine)
[2011, 27(1):103-110]

Cited: 18 times

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Long chain acyl-CoA synthetase-3 is a molecular target for peroxisome proliferator-activated receptor delta in HepG2 hepatoma cells.

Aiqin Cao, Hai Li, Yue Zhou, Minhao Wu, Jingwen Liu,

ACSL3 is a member of the long chain acyl-CoA synthetase (ACSL) family that plays key roles in fatty acid metabolism in various tissues in an isozyme-specific manner. Our previous studies showed that ACSL3 was transcriptionally up-regulated by the cytokine oncostatin M (OSM) in HepG2 cells, accompanied by reduced cellular triglyceride ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2010, 285(22):16664-16674]

Cited: 23 times

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Molecular dissection of human oncostatin M-mediated signal transductions through site-directed mutagenesis.

Haiyan Liu, Cristina Fenollar-Ferrer, Aiqin Cao, Claudio Anselmi, Paolo Carloni, Jingwen Liu,

The binding of oncostatin M (OM) to type I and type II receptor complexes elicits various biological responses by activating MEK/ERK and JAK/STAT signaling pathways. Some OM effects are clinically desirable such as reducing hyperlipidemia through the activation of hepatic LDL receptor transcription, a downstream event of ERK activation. The ... Read more >>

Int J Mol Med (International journal of molecular medicine)
[2009, 23(2):161-172]

Cited: 4 times

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Biochemical and molecular analysis of LePS2;1: a phosphate starvation induced protein phosphatase gene from tomato.

James C Baldwin, Athikkattuvalasu S Karthikeyan, Aiqin Cao, Kashchandra G Raghothama,

Adaptation of plants to phosphate (Pi) deficiency is a complex process involving host of biochemical changes. These changes are integrated at transcriptional level by Pi starvation mediated signal transduction pathway. Many of the signaling processes are regulated by reversible protein phosphorylation directed by protein kinases and protein phosphatases. In this ... Read more >>

Planta (Planta)
[2008, 228(2):273-280]

Cited: 15 times

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Phosphate differentially regulates 14-3-3 family members and GRF9 plays a role in Pi-starvation induced responses.

Aiqin Cao, Ajay Jain, James C Baldwin, Kashchandra G Raghothama,

The 14-3-3s are phosphoserine-binding proteins that act as key regulators of many metabolic pathways. Several biotic and abiotic stresses have been shown to modulate the expression of 14-3-3 genes. In Arabidopsis thaliana, 15 genes are known to code for 14-3-3 isoforms belonging to epsilon and non-epsilon groups. Since phosphorus is ... Read more >>

Planta (Planta)
[2007, 226(5):1219-1230]

Cited: 19 times

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