Article
Hematology
Nicolas Gendron, Mickael Rosa, Adeline Blandinieres, Yoann Sottejeau, Elisa Rossi, Eric Van Belle, Salim Idelcadi, Severine Lecourt, Andre Vincentelli, Audrey Cras, Ramadan Jashari, Richard Chocron, Yael Baudouin, Thibault Pamart, Ivan Bieche, Nathalie Nevo, Bernard Cholley, Jeanne Rancic, Bart Staels, Pascale Gaussem, Annabelle Dupont, Alain Carpentier, Sophie Susen, David M. Smadja
Summary: The study demonstrated that human VICs isolated from patients with calcific aortic valve disease have the potential to participate in aortic valve angiogenesis by differentiating into perivascular cells and exerting paracrine effects of VEGF-A. These findings suggest a novel function of VICs in valve vascularization during calcific aortic valve disease and highlight the importance of targeting perivascular differentiation and VEGF-A in slowing disease progression.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Article
Pharmacology & Pharmacy
Yuming Huang, Ming Liu, Chungeng Liu, Nianguo Dong, Liang Chen
Summary: This study found that andrographolide (AGP) can delay the progression of calcific aortic valve disease (CAVD) by inhibiting cell proliferation. AGP has the potential to prevent the occurrence of CAVD by regulating cell proliferation, making it a promising treatment option.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Wangxing Hu, Rongrong Wu, Chenyang Gao, Feng Liu, Zhiru Zeng, Qifeng Zhu, Jinyong Chen, Si Cheng, Kaixiang Yu, Yi Qian, Jing Zhao, Shuhan Zhong, Qingju Li, Lihan Wang, Xianbao Liu, Jian'an Wang
Summary: This study reveals that ERRα plays a crucial role in CAVD by regulating the expression of Hmox1 which affects the calcification process of hVICs. ERRα and Hmox1 may be potential targets for the treatment of CAVD.
Article
Cardiac & Cardiovascular Systems
Subramanian Dharmarajan, Mei Y. Speer, Kate Pierce, Jake Lally, Elizabeth M. Leaf, Mu-En Lin, Marta Scatena, Cecilia M. Giachelli
Summary: In this study, it was found that aVICs and sinus wall cells give rise to Runx2+ osteochondrogenic cells in diseased mouse aortic valves. Conditional depletion of Runx2 in specific cells led to decreased osteochondrogenic gene expression and improved aortic valve function in a mouse model of CAVD with high prevalence of hemodynamic valve dysfunction. Leaflet hinge and sinus wall calcification were significantly decreased following Runx2 depletion, suggesting a potential causal role in valve dysfunction.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2021)
Article
Engineering, Biomedical
Kathrin Stadelmann, Adrian Weghofer, Max Urbanczyk, Tengku Ibrahim Maulana, Peter D. Loskill, Peter D. Jones, Katja Schenke-Layland
Summary: This study developed a 3D in vitro model of the aortic heart valve that resembles the morphology and behavior of the native valve. It used a bi-layered electrospun scaffold to allow the growth of valvular endothelial cells and valvular interstitial cells, and successfully performed calcification studies.
ACTA BIOMATERIALIA
(2022)
Article
Physiology
Robin Tuscher, Alex Khang, Toni M. West, Chiara Camillo, Giovanni Ferrari, Michael S. Sacks
Summary: Calcific aortic valve disease (CAVD) is a progressive disease characterized by stiffening of the aortic valve tissues. Bicuspid aortic valve (BAV) is a congenital defect which leads to earlier development of CAVD. Surgical replacement is the current treatment for CAVD, but no pharmaceutical therapies or alternative treatments are available. This study aims to understand the biophysical changes in aortic valve interstitial cells (AVICs) in different CAVD states.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Jiaying Li, Qingchun Zeng, Zhenyu Xiong, Gaopeng Xian, Zuheng Liu, Qiong Zhan, Wenyan Lai, Lihua Ao, Xianzhong Meng, Hao Ren, Dingli Xu
Summary: Recent studies have shown that the choline-derived metabolite trimethylamine N-oxide (TMAO) promotes cardiovascular disease through inducing inflammation and stress, with higher TMAO levels found in patients with calcified aortic valve disease (CAVD). Experiment results indicate that TMAO induces osteogenic differentiation of aortic valve interstitial cells through endoplasmic reticulum and mitochondrial stress pathways, as demonstrated in both in vitro and in vivo experiments.
CARDIOVASCULAR RESEARCH
(2022)
Article
Cardiac & Cardiovascular Systems
D. Nehl, P. R. Goody, K. Maus, A. Pfeifer, E. Aikawa, F. Bakthiary, S. Zimmer, G. Nickenig, F. Jansen, M. R. Hosen
Summary: This study presents a unique technique to isolate specific human and porcine aortic valve cells and compares the characteristics of valvular interstitial cells (VICs) and endothelial cells (VECs) between these species for the first time. The results show that VECs are more migratory than VICs and can undergo endothelial-to-mesenchymal transition (EndMT) induction, leading to increased expression of EndMT markers. In addition, VICs demonstrate calcification ability. This study helps standardize the isolation technique for aortic valve cells and identifies porcine cells as an alternative cellular model system when human tissue is difficult to obtain.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Article
Cell Biology
Qian Zhou, Hong Cao, Xiaoyi Hang, Huamin Liang, Miaomiao Zhu, Yixian Fan, Jiawei Shi, Nianguo Dong, Ximiao He
Summary: The study utilized single-cell RNA sequencing to describe cellular diversity and interactions in CAVD, identifying potential treatment targets for interfering with EndMT progression and preventing VICs calcification. It highlights the importance of intercellular communication and the role of MDK as a potential novel inhibitor for CAVD.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Ming Fang, Bin Li, Xinming Li, Yudai Wang, Yu Zhuang
Summary: In this study, it was found that NLRP3 was highly expressed and SOCS1 was downregulated in patients and models with CAVD. Further investigation revealed that miR-29b participated in the NLRP3-regulated CAVD pathway through its target gene STAT3. Lastly, a miR-29b inhibitor was able to mitigate osteogenic differentiation and pyroptosis, while SOCS1 negatively regulated these processes in CAVD.
INTERNATIONAL JOURNAL OF CARDIOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Ming Fang, Bin Li, Xinming Li, Yudai Wang, Yu Zhuang
Summary: This study found that NLRP3-related genes are highly expressed in CAVD, while the expression of SOCS1 is reduced. MiR-29b participates in the NLRP3-regulated CAVD pathway and reverses osteoblastic differentiation of aortic valve interstitial cells by regulating pyroptosis and inhibiting inflammation via the STAT3/SOCS1 pathway. Furthermore, a miR-29b inhibitor can mitigate the increases in osteogenic differentiation and pyroptosis in CAVD.
INTERNATIONAL JOURNAL OF CARDIOLOGY
(2023)
Review
Biophysics
Brennan J. Vogl, Nicholas R. Niemi, Leigh G. Griffiths, Mohamad A. Alkhouli, Hoda Hatoum
Summary: The aortic valve is a complex structure affected by multiple factors, with diseases such as calcific aortic valve disease (CAVD) requiring a comprehensive consideration of molecular, tissue, and mechanical factors. Research focuses on understanding the biomechanical loads on the aortic valve, as well as strategies to combat CAVD.
BIOMECHANICS AND MODELING IN MECHANOBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Haiyan Zhou, Tangting Chen, Yongjie Li, Jingcan You, Xin Deng, Ni Chen, Tian Li, Youkun Zheng, Rong Li, Mao Luo, Jianbo Wu, Liqun Wang
Summary: This study found that Tie-2 is modified by AGEs in diabetes, leading to the inhibition of Ang-1 signaling activation and angiogenesis. This finding provides a novel mechanism for Ang-1/Tie-2 signal dysfunction and angiogenesis failure in diabetic ischemic diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cardiac & Cardiovascular Systems
Nalin H. Dayawansa, Sara Baratchi, Karlheinz Peter
Summary: Calcific aortic valve disease (CAVD) is a common acquired valvulopathy that lacks effective medical therapies. Mechanical stress and mechanosensing play critical roles in the perpetuation of valvular inflammation, and targeting mechanosensing pathways may provide promising interventions and prognostic biomarkers for CAVD management.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Cardiac & Cardiovascular Systems
Changdong Zhang, Mei Liu, Xueli Wang, Song Chen, Xiaojuan Fu, Geng Li, Nianguo Dong, Xiaoke Shang
Summary: In this study, it was found that CircANKRD36 can inhibit the expression of miR-599 and the activation of the TGF-beta signaling pathway, thereby affecting cell heterogeneity and endothelial mesenchymal transition in aortic valve stromal cells. This provides a new theoretical basis for treating calcific aortic valve disease (CAVD).
INTERNATIONAL JOURNAL OF CARDIOLOGY
(2022)
Article
Materials Science, Biomaterials
Reid L. Wilson, Jennifer P. Connell, K. Jane Grande-Allen
ACS BIOMATERIALS SCIENCE & ENGINEERING
(2019)
Letter
Surgery
Elizabeth L. Godfrey, Tahir H. Malik, Jennifer C. Lai, Ayse L. Mindikoglu, N. Thao N. Galvan, Ronald T. Cotton, Christine A. O'Mahony, John A. Goss, Abbas Rana
AMERICAN JOURNAL OF TRANSPLANTATION
(2020)
Article
Cardiac & Cardiovascular Systems
Syed Shahyan Bakhtiyar, Elizabeth L. Godfrey, Shayan Ahmed, Harveen Lamba, Jeffrey Morgan, Gabriel Loor, Andrew Civitello, Faisal H. Cheema, Whitson B. Etheridge, John Goss, Abbas Rana
Article
Engineering, Biomedical
Reid L. Wilson, Sarah A. Hewes, Anubama Rajan, Shih-Ching Lin, Carolyn Bomidi, Takanori Iida, Mary K. Estes, Anthony W. Maresso, K. Jane Grande-Allen
Summary: Researchers have developed a simple-to-use perfusion system to study the effects of invasive diarrheal pathogens in the human intestine; they found that infection simulation using this system displays important differences and in some ways better replicates the pathophysiology of in vivo infections; in addition, commensal strains can be added to the system to simulate the effects of the host microbiome on the infectious process.
ANNALS OF BIOMEDICAL ENGINEERING
(2021)
Article
Pediatrics
Tahir Malik, Manasi Joshi, Elizabeth Godfrey, Thao Galvan, Christine A. O'Mahony, Ronald Cotton, John Goss, Abbas Rana
Summary: The study demonstrates that pDSRI successfully predicts the risk of pediatric liver allograft discard using 11 significant risk factors, including DCD, elevated total bilirubin, and high alanine transaminase levels. The risk score model shows high accuracy in both the training and validation sets, potentially maximizing donor yield.
PEDIATRIC TRANSPLANTATION
(2021)
Article
Multidisciplinary Sciences
Mollie M. Smoak, Katie J. Hogan, K. Jane Grande-Allen, Antonios G. Mikos
Summary: This study assesses the potential of electrospun decellularized skeletal muscle extracellular matrix (dECM) to control mouse myoblast growth and myotube formation, aiming to develop a tissue-engineered therapy for skeletal muscle regeneration. The fabrication of a bioactive dECM-based system with tunable physicochemical properties has applications in skeletal muscle engineering, bringing the field closer to developing a therapy to address unmet clinical needs.
Article
Engineering, Biomedical
Amadeus S. Zhu, Tasneem Mustafa, Jennifer P. Connell, K. Jane Grande-Allen
Summary: Mitral valve disease is a common cardiovascular condition characterized by fibrotic remodeling. In this study, it was found that pro-inflammatory cytokines TNF-alpha and IL-1 beta can downregulate myofibroblast differentiation in mitral VICs via the NF-kappa B signaling pathway, suggesting potential new avenues for pharmaceutical treatments for mitral valve disease.
ACTA BIOMATERIALIA
(2021)
Article
Engineering, Mechanical
S. M. Mehta, D. R. De Santos, S. Sridhar, V. C. Aguayo, C. A. Meraz, M. Mikos, K. J. Grande-Allen
Summary: A small mechanical testing device was successfully developed by the research team, capable of conducting mechanical and microstructural characterization on a microscope stage, accurately testing mechanical properties of various soft materials with competitive performance and pricing. This innovation bridges the gap in testing microstructural changes left by existing commercial devices, providing a new research tool for the field of Biomedical Engineering.
EXPERIMENTAL TECHNIQUES
(2022)
Article
Pediatrics
Brian Hickner, Adrish Anand, Elizabeth L. Godfrey, Jordan Dunson, Ross M. Reul, Ronald Cotton, Nhu Thao Nguyen Galvan, Christine O'Mahony, John A. Goss, Abbas Rana
Summary: The intent-to-treat survival rate has steadily improved for heart, liver, and kidney transplants in children, indicating progress in pediatric transplantation. However, the percentage of patients transplanted within one year only significantly increased in heart transplant cases.
Article
Engineering, Biomedical
Matthew L. Bedell, Ziwen Wang, Katie J. Hogan, Angelica L. Torres, Hannah A. Pearce, Letitia K. Chim, K. Jane Grande-Allen, Antonios G. Mikos
Summary: Extrusion bioprinted constructs with different fiber architectures were fabricated to study their effects on encapsulated human mesenchymal stem cells' tissue-specific matrix deposition and integration. The gradient fiber (G-Fib) architecture showed increased chondral integration over time, while the segmented fiber (S-Fib) architecture was associated with significant mineralization. Both architectures demonstrated similar cartilage integration as re-inserted tissue controls. The study highlights the importance of considering spatial architecture in the engineering of multi-phasic tissue environments.
ACTA BIOMATERIALIA
(2023)
Meeting Abstract
Surgery
H. Oden-Brunson, E. Godfrey, H. Flores, A. Rana
AMERICAN JOURNAL OF TRANSPLANTATION
(2021)
Article
Nanoscience & Nanotechnology
Madeleine A. Roseen, Monica M. Fahrenholtz, Jennifer P. Connell, Kathryn Jane Grande-Allen
ACS APPLIED BIO MATERIALS
(2020)
Article
Nanoscience & Nanotechnology
Madeleine A. Roseen, Romi Lee, Allison D. Post, Megan Wancura, Jennifer P. Connell, Elizabeth Cosgriff-Hemandez, K. Jane Grande Allen
ACS APPLIED BIO MATERIALS
(2020)
Meeting Abstract
Cardiac & Cardiovascular Systems
W. C. Frankel, E. L. Godfrey, E. E. Suarez, A. Rana, A. E. Shafii, G. Loor, K. K. Liao
JOURNAL OF HEART AND LUNG TRANSPLANTATION
(2020)
Meeting Abstract
Cardiac & Cardiovascular Systems
E. L. Godfrey, W. C. Frankel, A. Rana, K. K. Liao, G. Loor, E. E. Suarez
JOURNAL OF HEART AND LUNG TRANSPLANTATION
(2020)