Hongyu Qiu

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Journals/Publications

• Guo, D., Zhu, W., & Qiu, H. (2024). C-C Motif Chemokine Ligand 2 and Chemokine Receptor 2 in Cardiovascular and Neural Aging and Aging-Related Diseases. International journal of molecular sciences, 25(16).
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  Aging is a prominent risk factor for numerous chronic diseases. Understanding the shared mechanisms of aging can aid in pinpointing therapeutic targets for age-related disorders. Chronic inflammation has emerged as a pivotal mediator of aging and a determinant in various age-related chronic conditions. Recent findings indicate that C-C motif chemokine ligand 2 and receptor 2 (CCL2-CCR2) signaling, an important physiological modulator in innate immune response and inflammatory defense, plays a crucial role in aging-related disorders and is increasingly recognized as a promising therapeutic target, highlighting its significance. This review summarizes recent advances in the investigation of CCL2-CCR2 signaling in cardiovascular and neural aging, as well as in various aging-related disorders. It also explores the underlying mechanisms and therapeutic potentials in these contexts. These insights aim to deepen our understanding of aging pathophysiology and the development of aging-related diseases.
• Shi, X., O'Connor, M., & Qiu, H. (2024). Valosin-containing protein acts as a target and mediator of S-nitrosylation in the heart through distinct mechanisms. Redox biology, 72, 103166.
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  S-nitrosylation (SNO) is an emerging paradigm of redox signaling protecting cells against oxidative stress in the heart. Our previous studies demonstrated that valosin-containing protein (VCP), an ATPase-associated protein, is a vital mediator protecting the heart against cardiac stress and ischemic injury. However, the molecular regulations conferred by VCP in the heart are not fully understood. In this study, we explored the potential role of VCP in cardiac protein SNO using multiple cardiac-specific genetically modified mouse models and various analytical techniques including biotin switch assay, liquid chromatography, mass spectrometry, and western blotting. Our results showed that cardiac-specific overexpression of VCP led to an overall increase in the levels of SNO-modified cardiac proteins in the transgenic (TG) vs. wild-type (WT) mice. Mass spectrometry analysis identified mitochondrial proteins involved in respiration, metabolism, and detoxification as primary targets of SNO modification in VCP-overexpressing mouse hearts. Particularly, we found that VCP itself underwent SNO modification at a specific cysteine residue in its N-domain. Additionally, our study demonstrated that glyceraldehyde 3-phosphate dehydrogenase (GAPDH), a key enzyme in glycolysis, also experienced increased SNO in response to VCP overexpression. While deletion of inducible nitric oxide synthase (iNOS) in VCP TG mice did not affect VCP SNO, it did abolish SNO modification in mitochondrial complex proteins, suggesting a dual mechanism of regulation involving both iNOS-dependent and independent pathways. Overall, our findings shed light on post-translational modification of VCP in the heart, unveiling a previously unrecognized role for VCP in regulating cardiac protein SNO and offering new insights into its function in cardiac protection.
• Sun, X., Tang, X., & Qiu, H. (2024). Cardiac-Specific Suppression of Valosin-Containing Protein Induces Progressive Heart Failure and Premature Mortality Correlating with Temporal Dysregulations in mTOR Complex 2 and Protein Phosphatase 1. International journal of molecular sciences, 25(12).
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  Valosin-containing protein (VCP), an ATPase-associated protein, is emerging as a crucial regulator in cardiac pathologies. However, the pivotal role of VCP in the heart under physiological conditions remains undetermined. In this study, we tested a hypothesis that sufficient VCP expression is required for cardiac development and physiological cardiac function. Thus, we generated a cardiac-specific VCP knockout (KO) mouse model and assessed the consequences of VCP suppression on the heart through physiological and molecular studies at baseline. Our results reveal that homozygous KO mice are embryonically lethal, whereas heterozygous KO mice with a reduction in VCP by ~40% in the heart are viable at birth but progressively develop heart failure and succumb to mortality at the age of 10 to 12 months. The suppression of VCP induced a selective activation of the mammalian target of rapamycin complex 1 (mTORC1) but not mTORC2 at the early age of 12 weeks. The prolonged suppression of VCP increased the expression (by ~2 folds) and nuclear translocation (by >4 folds) of protein phosphatase 1 (PP1), a key mediator of protein dephosphorylation, accompanied by a remarked reduction (~80%) in AKTSer473 phosphorylation in VCP KO mouse hearts at a later age but not the early stage. These temporal molecular alterations were highly associated with the progressive decline in cardiac function. Overall, our findings shed light on the essential role of VCP in the heart under physiological conditions, providing new insights into molecular mechanisms in the development of heart failure.
• Visconti, A., & Qiu, H. (2024). Recent advances in serum response factor posttranslational modifications and their therapeutic potential in cardiovascular and neurological diseases. Vascular pharmacology, 156, 107421.
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  Serum Response Factor (SRF) is a key regulatory transcription factor present in various cell types throughout the body, playing essential roles in cellular functions under physiological conditions. Mutations and abnormal expression of SRF have been linked to the development of various diseases and disorders. Recent evidence highlights that post-translational modifications (PTMs) are critical for regulating SRF function in different cell types and contribute to disease pathogenesis. Targeting SRF-related PTMs is emerging as a promising therapeutic approach for treating SRF-associated diseases. In this review, we summarize recent advances in understanding SRF PTMs and their underlying regulatory mechanisms. We also explore the implications of SRF-PTM in related cardiovascular and neurological diseases and their potential for therapeutic intervention. This information underscores the significance of SRF PTMs in both physiological and pathological contexts, enhancing our understanding of disease mechanisms and paving the way for the development of novel therapeutic strategies.
• Wong, D., & Qiu, H. (2024). New insights into the pharmacological inhibition of SRF activity: Key inhibitory targets and mechanisms. Vascular pharmacology, 157, 107443.
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  Serum Response Factor (SRF) is a critical regulatory transcription factor widely expressed across cell types and is essential for animal survival. Excessive SRF activity has been linked to various pathological conditions and diseases, including cardiovascular diseases, cancers and neurodegenerative disorders, making the inhibition of SRF hyperactivity a promising therapeutic strategy. This review summarizes recent advancements in the discovery and development of SRF inhibitors, their regulatory mechanisms, and their respective molecular foundations. These insights deepen our understanding of current therapeutic potentials, paving the way for novel approaches to treat diseases associated with SRF hyperactivity.
• Qiu, H. (2023). A potential mediator of aging-related vascular pathologies. Vascul Pharmacol., 152, 107231. doi:10.1016/j.vph.2023.107213
• Qiu, H. (2023). Editorial: Women in cardiovascular therapeutics. Front Cardiovasc Med, 10, 1183472. doi:10.3389/fcvm.2023.1183427
• Qiu, H. (2023). Epigenetic Reader Bromodomain-Containing Protein 4 in Aging-Related Vascular Pathologies and Diseases: Molecular Basis, Functional Relevance, and Clinical Potential. Biomolecules. doi:10.3390/biom13071135
• Qiu, H. (2023). Reprogramming of human peripheral blood mononuclear cells into induced mesenchymal stromal cells using non-integrating vectors.
  . Commun Biol., 6, 393. doi:10.1038/s42003-023-04737-x