Micro- and nanoscale biophysical cues for cardiovascular disease therapy

Mohindra, Priya; Desai, Tejal A.

doi:10.1016/j.nano.2021.102365

Cited by 13 publications

(9 citation statements)

References 193 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CVDs are still the leading cause of death worldwide, bringing a heavy health and economic burden to the world. 49 Acrolein is a common F I G U R E 5 Effects of acrolein on DNA damage response (DDR) pathway in human umbilical vein endothelial cells (HUVECs). (A) Western blot analysis of γ-H2AX, H2AX, p-Ataxia-Telangiectasia-Mutated (ATM), ATM, Chk2, p-ATM and Rad-3-related (ATR), ATR, Chk1, Cyclin B1, p53, and p21.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of acrolein induces toxicity in human umbilical vein endothelial cells: Oxidative stress, DNA damage response, and apoptosis

Liú

Cheng

Mei

et al. 2021

Environmental Toxicology

View full text Add to dashboard Cite

Acrolein is a ubiquitous environmental pollutant that produced by the incomplete combustion of cigarette smoke, forest fires, petroleum fuels, plastic materials, and cooking fumes. Inhalation is a common form of people exposure to acrolein, increasing evidence demonstrates that acrolein impairs the cardiovascular system by targeting vascular endothelial cells. However, the molecular mechanism of the cytotoxicity of acrolein exposure on vascular endothelial cells remains unclear. This work focused on the toxicity of acrolein on human umbilical vein endothelial cells (HUVECs). The molecular mechanism was studied based on oxidative stress, DNA damage response (DDR), and mitochondrial apoptosis pathways. After HUVECs were treated with 12.5, 25, and 50 μM acrolein for 24 h, cell viability, cell colony formation, mitochondrial membrane potential, and adenosine triphosphate content significantly reduced, and acrolein increased intracellular reactive oxygen species, apoptosis rate, and 8-hydroxy-2 deoxyguanosine (8-OHdG) level. Furthermore, p38MAPK and c-Jun N-terminal kinase signaling pathways were activated in response to oxidative stress. Moreover, acrolein induced G0/G1phase arrest, promoted the expression of γ-H2AX, activated the DDR signaling pathway (Ataxia-Telangiectasia-Mutated [ATM] and Rad-3-related/Chk1 and ATM/Chk2), and triggered the consequent cell cycle checkpoints. Finally, the protein expression of Bax/Bcl-2 and cleaved Caspase-3 was up-regulated, suggesting apoptosis was induced by triggering the mitochondrial apoptosis pathway. All these results indicated that acrolein induced HUVECs cytotoxicity by regulating oxidative stress, DNA damage, and apoptosis. This study provides a novel perspective on the mechanism of acrolein-induced cardiovascular toxicity, it will be helpful for the prevention of acrolein-induced cardiovascular disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Mechanisms of acrolein induces toxicity in human umbilical vein endothelial cells: Oxidative stress, DNA damage response, and apoptosis

Liú

Cheng

Mei

et al. 2021

Environmental Toxicology

View full text Add to dashboard Cite

show abstract

“…AMI can lead to cardiomyocyte death, often followed by a robust inflammatory response in myocardial tissue. Previous studies have demonstrated that the activation of complement and Toll-like receptor (TLR)/interleukin-1 (IL-1) signaling is involved in the onset and development of inflammation [12][13][14]. A suitable inflammatory response is beneficial for the healing of injured myocardial tissue, indicating that the body performs the function of self-repair.…”

Section: Introductionmentioning

confidence: 99%

Inflammation and Oxidative Stress Role of S100A12 as a Potential Diagnostic and Therapeutic Biomarker in Acute Myocardial Infarction

Xie

Luo

et al. 2022

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Acute myocardial infarction (AMI) is one of the most serious cardiovascular diseases with high morbidity and mortality. Numerous studies have indicated that S100A12 may has an essential role in the occurrence and development of AMI, and in-depth studies are currently lacking. The purpose of this study is to investigate the effect of S100A12 on inflammation and oxidative stress and to determine its clinical applicability in AMI. Here, AMI datasets used to explore the expression pattern of S100A12 in AMI were derived from the Gene Expression Omnibus (GEO) database. The pooled standard average deviation (SMD) was calculated to further determine S100A12 expression. The overlapping differentially expressed genes (DEGs) contained in all included datasets were recognized by the GEO2R tool. Then, functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, were carried out to determine the molecular function of overlapping DEGs. Gene set enrichment analysis (GSEA) was conducted to determine unrevealed mechanisms of S100A12. Summary receiver operating characteristic (SROC) curve analysis and receiver operating characteristic (ROC) curve analysis were carried out to identify the diagnostic capabilities of S100A12. Moreover, we screened miRNAs targeting S100A12 using three online databases (miRWalk, TargetScan, and miRDB). In addition, by comprehensively using enzyme-linked immunosorbent assay (ELISA), real-time quantitative PCR (RT–qPCR), Western blotting (WB) methods, etc., we used the AC16 cells to validate the expression and underlying mechanism of S100A12. In our study, five datasets related to AMI, GSE24519, GSE60993, GSE66360, GSE97320, and GSE48060 were included; 412 overlapping DEGs were identified. Protein-protein interaction (PPI) network and functional analyses showed that S100A12 was a pivotal gene related to inflammation and oxidative stress. Then, S100A12 overexpression was identified based on the included datasets. The pooled standard average deviation (SMD) also showed that S100A12 was upregulated in AMI ( SMD = 1.36 , 95% CI: 0.70-2.03, p = 0.024 ). The SROC curve analysis result suggested that S100A12 had remarkable diagnostic ability in AMI ( AUC = 0.90 , 95% CI: 0.87-0.92). And nine miRNAs targeting S100A12 were also identified. Additionally, the overexpression of S100A12 was further confirmed that it maybe promote inflammation and oxidative stress in AMI through comprehensive in vitro experiments. In summary, our study suggests that overexpressed S100A12 may be a latent diagnostic biomarker and therapeutic target of AMI that induces excessive inflammation and oxidative stress. Nine miRNAs targeting S100A12 may play a crucial role in AMI, but further studies are still needed. Our work provides a positive inspiration for the in-depth study of S100A12 in AMI.

show abstract

“…60,61 Typically, these contact guidance cues can either be on the nano scale like collagen bundles (120-150 nm) or on the micron scale such as grooves and pillars (10-250 μm). Both micro-and nanoscale topographical patterns have been shown to influence cell orientation, adhesion, and morphology, 62 and many researchers use micro-topographies due to their simplicity and ease of control. For example, Shi et al developed an elastomeric PDMS film using soft lithography to generate surface patterns.…”

Section: Significant Advancements Have Been Made In Building Cardiacmentioning

confidence: 99%

Elastomeric platform with surface wrinkling patterns to control cardiac cell alignment

House

Cornick

Butt

et al. 2023

J Biomedical Materials Res

View full text Add to dashboard Cite

There is a growing interest in creating 2D cardiac tissue models that display native extracellular matrix (ECM) cues of the heart tissue. Cellular alignment alone is known to be a crucial cue for cardiac tissue development by regulating cell–cell and cell‐ECM interactions. In this study, we report a simple and robust approach to create lamellar surface wrinkling patterns enabling spatial control of pattern dimensions with a wide range of pattern amplitude (A ≈ 2–55 μm) and wavelength (λ ≈ 35–100 μm). For human cardiomyocytes (hCMs) and human cardiac fibroblasts (hCFs), our results indicate that the degree of cellular alignment and pattern recognition are correlated with pattern A and λ. We also demonstrate fabrication of devices composed of micro‐well arrays with user‐defined lamellar patterns on the bottom surface of each well for high‐throughput screening studies. Results from a screening study indicate that cellular alignment is strongly diminished with increasing seeding density. In another study, we show our ability to vary hCM/hCF seeding ratio for each well to create co‐culture systems where seeding ratio is independent of cellular alignment.

show abstract

Micro- and nanoscale biophysical cues for cardiovascular disease therapy

Cited by 13 publications

References 193 publications

Mechanisms of acrolein induces toxicity in human umbilical vein endothelial cells: Oxidative stress, DNA damage response, and apoptosis

Mechanisms of acrolein induces toxicity in human umbilical vein endothelial cells: Oxidative stress, DNA damage response, and apoptosis

Inflammation and Oxidative Stress Role of S100A12 as a Potential Diagnostic and Therapeutic Biomarker in Acute Myocardial Infarction

Elastomeric platform with surface wrinkling patterns to control cardiac cell alignment

Contact Info

Product

Resources

About