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JACC. CardioOncology Dec 2023Despite improvements in cancer survival, cancer therapy-related cardiovascular toxicity has risen to become a prominent clinical challenge. This has led to the growth of... (Review)
Review
Despite improvements in cancer survival, cancer therapy-related cardiovascular toxicity has risen to become a prominent clinical challenge. This has led to the growth of the burgeoning field of cardio-oncology, which aims to advance the cardiovascular health of cancer patients and survivors, through actionable and translatable science. In these Global Cardio-Oncology Symposium 2023 scientific symposium proceedings, we present a focused review on the mechanisms that contribute to common cardiovascular toxicities discussed at this meeting, the ongoing international collaborative efforts to improve patient outcomes, and the bidirectional challenges of translating basic research to clinical care. We acknowledge that there are many additional therapies that are of significance but were not topics of discussion at this symposium. We hope that through this symposium-based review we can highlight the knowledge gaps and clinical priorities to inform the design of future studies that aim to prevent and mitigate cardiovascular disease in cancer patients and survivors.
PubMed: 38205010
DOI: 10.1016/j.jaccao.2023.08.003 -
Cellular and Molecular Life Sciences :... Aug 2023Exposure to chronic psychological stress (CPS) is an intractable risk factor for inflammatory and metabolic diseases. Lysosomal cysteinyl cathepsins play an important...
Exposure to chronic psychological stress (CPS) is an intractable risk factor for inflammatory and metabolic diseases. Lysosomal cysteinyl cathepsins play an important role in human pathobiology. Given that cathepsin S (CTSS) is upregulated in the stressed vascular and adipose tissues, we investigated whether CTSS participates in chronic stress-induced skeletal muscle mass loss and dysfunction, with a special focus on muscle protein metabolic imbalance and apoptosis. Eight-week-old male wildtype (CTSS) and CTSS-knockout (CTSS) mice were randomly assigned to non-stress and variable-stress groups. CTSS stressed mice showed significant losses of muscle mass, dysfunction, and fiber area, plus significant mitochondrial damage. In this setting, stressed muscle in CTSS mice presented harmful alterations in the levels of insulin receptor substrate 2 protein content (IRS-2), phospho-phosphatidylinositol 3-kinase, phospho-protein kinase B, and phospho-mammalian target of rapamycin, forkhead box-1, muscle RING-finger protein-1 protein, mitochondrial biogenesis-related peroxisome proliferator-activated receptor-γ coactivator-α, and apoptosis-related B-cell lymphoma 2 and cleaved caspase-3; these alterations were prevented by CTSS deletion. Pharmacological CTSS inhibition mimics its genetic deficiency-mediated muscle benefits. In CC cells, CTSS silencing prevented stressed serum- and oxidative stress-induced IRS-2 protein reduction, loss of the myotube myosin heavy chain content, and apoptosis accompanied by a rectification of investigated molecular harmful changes; these changes were accelerated by CTSS overexpression. These findings demonstrated that CTSS plays a role in IRS-2-related protein anabolism and catabolism and cell apoptosis in stress-induced muscle wasting, suggesting a novel therapeutic strategy for the control of chronic stress-related muscle disease in mice under our experimental conditions by regulating CTSS activity.
Topics: Animals; Male; Mice; Adipose Tissue; Cathepsins; Muscles; Muscular Atrophy; Stress, Physiological
PubMed: 37589754
DOI: 10.1007/s00018-023-04888-4 -
Retinal Cases & Brief Reports Mar 2024To report a patient with Shwachman-Diamond syndrome and concomitant rod-cone dystrophy who underwent bone marrow transplantation.
PURPOSE
To report a patient with Shwachman-Diamond syndrome and concomitant rod-cone dystrophy who underwent bone marrow transplantation.
METHODS
Retrospective single case report.
RESULTS
A female patient with Shwachman-Diamond syndrome was referred to a tertiary hospital to investigate possible pigmentary retinopathy at the age of 16. She described poor night vision and was found to have reduced visual acuity (6/20 right, 6/38 left). Over the ten-year follow-up period, her visual acuity remained relatively stable with no new visual symptoms. Optical coherence tomography revealed progressive, diffuse outer retinal thinning with disruption of the ellipsoid zone, which initially was relatively preserved subfoveally. Fundus autofluorescence images revealed generalised areas of hypoautofluorescence beyond the vascular arcades and a perimacular ring of increased autofluorescence. The flash electroretinogram was in keeping with a severe rod-cone dystrophy. The pattern visual evoked potential was abnormal but detectable indicating macular pathway dysfunction, suggesting encroachment into central macular regions but with some functional preservation.
CONCLUSIONS
We report a patient with Shwachman-Diamond syndrome with severe early-onset rod-cone dystrophy noted at the age of 16. Slow anatomical progression has been observed over the subsequent ten years, with relative functional macular preservation to support a visual acuity of 6/36 in both eyes.
PubMed: 38437796
DOI: 10.1097/ICB.0000000000001568 -
Genes Jun 2024The ring finger protein 213 gene (RNF213) is involved in several vascular diseases, both intracranial and systemic ones. Some variants are common in the Asian population...
The ring finger protein 213 gene (RNF213) is involved in several vascular diseases, both intracranial and systemic ones. Some variants are common in the Asian population and are reported as a risk factor for moyamoya disease, intracranial stenosis and intracranial aneurysms. Among intracranial vascular diseases, both moyamoya disease and intracranial artery dissection are more prevalent in the Asian population. We performed a systematic review of the literature, aiming to assess the rate of RNF213 variants in patients with spontaneous intracranial dissections. Four papers were identified, providing data on 53 patients with intracranial artery dissection. The rate of RNF213 variants is 10/53 (18.9%) and it increases to 10/29 (34.5%), excluding patients with vertebral artery dissection. All patients had the RNF213 p.Arg4810Lys variant. RNF213 variants seems to be involved in intracranial dissections in Asian cohorts. The small number of patients, the inclusion of only patients of Asian descent and the small but non-negligible coexistence with moyamoya disease familiarity might be limiting factors, requiring further studies to confirm these preliminary findings and the embryological interpretation.
Topics: Humans; Adenosine Triphosphatases; Aortic Dissection; Asian People; Genetic Predisposition to Disease; Intracranial Aneurysm; Moyamoya Disease; Polymorphism, Single Nucleotide; Ubiquitin-Protein Ligases
PubMed: 38927660
DOI: 10.3390/genes15060725 -
European Journal of Pharmacology Nov 2023Pulmonary artery smooth muscle cells (PASMCs) phenotypic switching and pulmonary artery endothelial cells (PAECs) endothelial-mesenchymal transition (EndMT) are...
Pulmonary artery smooth muscle cells (PASMCs) phenotypic switching and pulmonary artery endothelial cells (PAECs) endothelial-mesenchymal transition (EndMT) are important in promoting pulmonary hypertension (PH)-pulmonary vascular remodeling (PVR). Resveratrol can efficiently inhibit the proliferation of PASMCs, but its application is limited due to its low bioavailability and solubility. In this study, we modified resveratrol to assess the role of A ring N(CH)-based derivatives of resveratrol (Res4) in PVR-PASMCs phenotypic switching and PVR-PAECs EndMT. Chemical methods were used for the preparation of Res4; NMRS and HPLC were used to authenticate Res4. Mice developed PVR after 4 weeks of hypoxia (10% O). Res4 (50 mg/kg/d) attenuated right ventricular systolic pressure, right ventricular hypertrophy, and PVR. PASMCs developed phenotypic switching and PAECs developed EndMT after 2 days of hypoxia (3% O). Res4 (10 μM) could inhibit PASMCs and PAECs viability. Res4 could decrease proliferating cell nuclear antigen (PCNA) and osteopontin (OPN) expression, and increase α-smooth muscle actin (α-SMA) and vimentin expression in PASMCs. It could also decrease PCNA, α-SMA, vimentin expression and increase platelet endothelial cell adhesion molecule (CD31) expression in PAECs. Notably, Res4 inhibited the phosphorylation levels of mitogen-activated protein kinase kinase (MEK), extracellular signal-regulated protein kinase (ERK), Jun-N-terminal kinase (JNK), and p38 kinase in hypoxia-treated PASMCs and PAECs, indicating MAPK pathway may be involved in Res4-induced inhibition of PASMCs phenotypic switching and PAECs EndMT. Our data demonstrated that Res4 exerts antiproliferative effects by regulating PASMCs phenotypic switching and PAECs EndMT. Res4 may be potentially used as a drug against PH-PVR.
Topics: Mice; Animals; Hypertension, Pulmonary; Proliferating Cell Nuclear Antigen; Resveratrol; Vimentin; Endothelial Cells; Vascular Remodeling; Hypoxia; Pulmonary Artery; Myocytes, Smooth Muscle; Cell Proliferation; Cells, Cultured
PubMed: 37820784
DOI: 10.1016/j.ejphar.2023.176077 -
Journal of Veterinary Science Sep 2023Kalkitoxin (KT) is an active lipopeptide isolated from the cyanobacterium found in the bed of the coral reef. Although KT suppresses cell division and inflammation,...
BACKGROUND
Kalkitoxin (KT) is an active lipopeptide isolated from the cyanobacterium found in the bed of the coral reef. Although KT suppresses cell division and inflammation, KT's mechanism of action in vascular smooth muscle cells (VSMCs) is unidentified. Therefore, our main aim was to investigate the impact of KT on vascular calcification for the treatment of cardiovascular disease.
OBJECTIVES
Using diverse calcification media, we studied the effect of KT on VSMC calcification and the underlying mechanism of this effect.
METHODS
VSMC was isolated from the 6 weeks ICR mice. Then VSMCs were treated with different concentrations of KT to check the cell viability. Alizarin red and von Kossa staining were carried out to examine the calcium deposition on VSMC. Thoracic aorta of 6 weeks mice were taken and treated with different concentrations of KT, and H and E staining was performed. Real-time polymerase chain reaction and western blot were performed to examine KT's effect on VSMC mineralization. Calcium deposition on VSMC was examined with a calcium deposition quantification kit.
RESULTS
Calcium deposition, Alizarin red, and von Kossa staining revealed that KT reduced inorganic phosphate-induced calcification phenotypes. KT also reduced Ca-induced calcification by inhibiting genes that regulate osteoblast differentiation, such as runt-related transcription factor 2 (RUNX-2), SMAD family member 4, osterix, collagen 1α, and osteopontin. Also, KT repressed Ca-induced bone morphogenetic protein 2, RUNX-2, collagen 1α, osteoprotegerin, and smooth muscle actin protein expression. Likewise, Alizarin red and von Kossa staining showed that KT markedly decreased the calcification of ring formation in the mouse thoracic aorta.
CONCLUSIONS
This experiment demonstrated that KT decreases vascular calcification and may be developed as a new therapeutic treatment for vascular calcification and arteriosclerosis.
Topics: Animals; Mice; Calcium; Cells, Cultured; Collagen; Mice, Inbred ICR; Muscle, Smooth, Vascular; Signal Transduction; Vascular Calcification
PubMed: 38031648
DOI: 10.4142/jvs.23148 -
Plant Science : An International... Feb 2024Trees play a pivotal role in terrestrial ecosystems as well as being an important natural resource. These attributes are primarily associated with the capacity of trees... (Review)
Review
Trees play a pivotal role in terrestrial ecosystems as well as being an important natural resource. These attributes are primarily associated with the capacity of trees to continuously produce woody tissue from the vascular cambium, a ring of stem cells located just beneath the bark. Long-lived trees are exposed to a myriad of biological and environmental stresses that may result in wounding, leading to a loss of bark and the underlying vascular cambium. This affects both wood formation and the quality of timber arising from the tree. In addition, the exposed wound site is a potential entry point for pathogens that cause disease. In response to wounding, trees have the capacity to regenerate lost or damaged tissues at this site. Investigating gene expression changes associated with different stages of wound healing reveals complex and dynamic changes in the activity of transcription factors, signalling pathways and hormone responses. In this review we summarise these data and discuss how they relate to our current understanding of vascular cambium formation and xylem differentiation during secondary growth. Based on this analysis, a model for wound healing that provides the conceptual foundations for future studies aimed at understanding this intriguing process is proposed.
Topics: Trees; Phloem; Ecosystem; Xylem; Wound Healing
PubMed: 38070652
DOI: 10.1016/j.plantsci.2023.111950 -
World Journal For Pediatric &... May 2024Circumflex aorta is described as a retroesophageal aortic arch, with opposite-sided descending aorta forming a true vascular ring with ligamentum arteriosum. We report...
Circumflex aorta is described as a retroesophageal aortic arch, with opposite-sided descending aorta forming a true vascular ring with ligamentum arteriosum. We report two cases of right-sided circumflex aorta with varied clinical presentation. Computed tomography diagnosed this vascular ring anomaly. The patients were managed with the aortic uncrossing procedure as a primary surgical strategy. Preoperative diagnosis and thorough planning were essential for the successful outcome. The patients did not have any residual symptoms of tracheal and esophageal compression on follow up.
Topics: Humans; Aorta, Thoracic; Tomography, X-Ray Computed; Male; Vascular Ring; Female; Vascular Surgical Procedures
PubMed: 37769607
DOI: 10.1177/21501351231196500 -
Nature Communications Apr 2024Heart failure with preserved ejection fraction (HFpEF) is associated with endothelial dysfunction. We have previously reported that statins prevent endothelial...
Heart failure with preserved ejection fraction (HFpEF) is associated with endothelial dysfunction. We have previously reported that statins prevent endothelial dysfunction through inhibition of microRNA-133a (miR-133a). This study is to investigate the effects and the underlying mechanisms of statins on HFpEF. Here, we show that statins upregulate the expression of a circular RNA (circRNA-RBCK1) which is co-transcripted with the ring-B-box-coiled-coil protein interacting with protein kinase C-1 (RBCK1) gene. Simultaneously, statins increase activator protein 2 alpha (AP-2α) transcriptional activity and the interaction between circRNA-RBCK1 and miR-133a. Furthermore, AP-2α directly interacts with RBCK1 gene promoter in endothelial cells. In vivo, lovastatin improves diastolic function in male mice under HFpEF, which is abolished by loss function of endothelial AP-2α or circRNA-RBCK1. This study suggests that statins upregulate the AP-2α/circRNA-RBCK1 signaling to suppress miR-133a in cardiac endothelial cells and prevent diastolic dysfunction in HFpEF.
Topics: Animals; Male; Mice; Endothelial Cells; Heart Failure; Hydroxymethylglutaryl-CoA Reductase Inhibitors; MicroRNAs; RNA, Circular; Stroke Volume
PubMed: 38580662
DOI: 10.1038/s41467-024-47327-z -
Cells Feb 2024Diabetic foot ulcers (DFU) pose a significant health risk in diabetic patients, with insufficient revascularization during wound healing being the primary cause. This...
The Combination of Vascular Endothelial Growth Factor A (VEGF-A) and Fibroblast Growth Factor 1 (FGF1) Modified mRNA Improves Wound Healing in Diabetic Mice: An Ex Vivo and In Vivo Investigation.
BACKGROUND
Diabetic foot ulcers (DFU) pose a significant health risk in diabetic patients, with insufficient revascularization during wound healing being the primary cause. This study aimed to assess microvessel sprouting and wound healing capabilities using vascular endothelial growth factor (VEGF-A) and a modified fibroblast growth factor (FGF1).
METHODS
An ex vivo aortic ring rodent model and an in vivo wound healing model in diabetic mice were employed to evaluate the microvessel sprouting and wound healing capabilities of VEGF-A and a modified FGF1 both as monotherapies and in combination.
RESULTS
The combination of VEGF-A and FGF1 demonstrated increased vascular sprouting in the ex vivo mouse aortic ring model, and topical administration of a combination of VEGF-A and FGF1 mRNAs formulated in lipid nanoparticles (LNPs) in mouse skin wounds promoted faster wound closure and increased neovascularization seven days post-surgical wound creation. RNA-sequencing analysis of skin samples at day three post-wound creation revealed a strong transcriptional response of the wound healing process, with the combined treatment showing significant enrichment of genes linked to skin growth.
CONCLUSION
f-LNPs encapsulating VEGF-A and FGF1 mRNAs present a promising approach to improving the scarring process in DFU.
Topics: Humans; Mice; Animals; Vascular Endothelial Growth Factor A; Fibroblast Growth Factor 1; Diabetes Mellitus, Experimental; Neovascularization, Physiologic; Wound Healing; Diabetic Foot; Disease Models, Animal
PubMed: 38474378
DOI: 10.3390/cells13050414