bims-evecad Biomed News
on Extracellular vesicles and cardiovascular disease
Issue of 2025–11–23
six papers selected by
Cliff Dominy
  1. Engineered endothelial cells targeting and dihydrotanshinone I loaded bacterial extracellular vesicles for atherosclerosis therapy.
  2. Targeted engineered exosomes alleviate myocardial infarction injury by enhancing angiogenesis and improving mitochondrial function.
  3. Mitochondrial stress bridge: Could muscle-derived extracellular vesicles be the missing link between sarcopenia, insulin resistance, and chemotherapy-induced cardiotoxicity?
  4. LincRNA-p21 drives apoptosis and calcification of vascular smooth muscle cell via small extracellular vesicles under hyperphosphatemic conditions in chronic kidney disease.
  5. Revealing the complexity of the epicardial secretome.
  6. Development of heparinized agarose microspheres for the recovery of exosomes curing acute myocardial infarction.
  1. Bioeng Transl Med. 2025 Nov;10(6): e70074
    Engineered endothelial cells targeting and dihydrotanshinone I loaded bacterial extracellular vesicles for atherosclerosis therapy.
    Rong-Rong Zhu, Xue-Liang Zhou, Yan-Wei Liu, Ri Xu, Peng Deng, Zhong-Yong Liu.
      Atherosclerosis (AS) is a complex cardiovascular disease characterized by endothelial dysfunction, dyslipidemia, and immune-inflammatory responses, leading to arterial plaque formation and potentially fatal complications such as myocardial infarction and stroke. Traditional treatments, such as statins, often pose challenges due to their side effects and limited efficacy. In this study, we explore a novel therapeutic approach utilizing engineered endothelial cells (ECs) targeting probiotic extracellular vesicles loaded with dihydrotanshinone I (DHT) (EC-BEVsDHT), a bioactive compound derived from Danshen (Salvia miltiorrhiza Bunge). With the characterization of EC-BEVsDHT by transmission electron microscope and nanoparticle tracking analysis, EC-BEVsDHT exhibited typical spherical morphology and particle size distribution. High-performance liquid chromatography coupled with tandem mass spectrometric confirmed the expression of the ECs-targeting peptide VSSSTPR in EC-BEVsDHT and EC-BEVsDHT. We further investigated the anti-atherosclerotic effects and molecular mechanisms of EC-BEVsDHT on human umbilical vein endothelial cells (HUVECs) and Apolipoprotein E-deficient (ApoE-/-) C57BL/6J mice. We found that EC-BEVsDHT attenuated oxidized low-density lipoprotein induced HUVECs injury in vitro and decreased AS in ApoE-/- mice in vivo. Our findings suggest that EC-BEVsDHT hold promise as a safe and effective therapeutic strategy for AS, offering potential advantages over traditional treatments.
    Keywords:  atherosclerosis; bacterial extracellular vesicles; dihydrotanshinone I; endothelial cells
    DOI:  https://doi.org/10.1002/btm2.70074
  2. J Control Release. 2025 Nov 14. pii: S0168-3659(25)01018-1. [Epub ahead of print] 114404
    Targeted engineered exosomes alleviate myocardial infarction injury by enhancing angiogenesis and improving mitochondrial function.
    Haixia Luo, Kexin Wang, Yan Zhang, Tiantian Li, Xiaojie Jia, Renqian Feng, Ran Zhao, Rui Yu, Lang Hu, Mingming Zhang, Bingchao Qi, Yan Li.
      Myocardial infarction (MI) remains a leading cause of global mortality, where acute ischemic injury and chronic cardiomyocyte dysfunction are pathological mechanisms leading to heart failure (HF). Current therapies fail to effectively halt this progression. Although VegfA delivery shows potential for revascularization, its clinical translation is limited by inefficient delivery systems. Exosomes, as emerging nanocarriers, hold promise but suffer from poor targeting. Here, a dual mRNA-loaded exosome platment (ExoIC-LNV) for synergistic therapy is developed. The exosome is functionally designed with ischemic myocardium targeting peptide (IMTP) and Connexin 43 (Cx43) to accumulate at the ischemic region. Meanwhile, ExoIC-LNV contains VegfA mRNA and Ndufs1 mRNA, based on the binding properties of L7Ae. The results demonstrate that ExoIC-LNV achieve significantly higher enrichment in ischemic tissue compared to single targeted modified exosomes. The Ndufs1-loaded exosomes improve mitochondrial function in hypoxic cardiomyocytes, and the VefgA-loaded exosomes promote angiogenesis in ischemic tissue. ExoIC-LNV loaded with dual mRNAs exhibit superior mitochondrial improvement while promoting angiogenesis, resulting in better cardiac function improvement through dual-pathway modulation after MI. Through multiple tail vein injections, the benefical proteins accumulate in the ischemic area, providing better prospects for clinical translation. This study proposes a targeted exosome-based strategy for combating pathological remodeling in MI and represents a possible approach for HF prevention.
    Keywords:  Angiogenesis; Exosomes; Mitochondria; Myocardial infraction
    DOI:  https://doi.org/10.1016/j.jconrel.2025.114404
  3. Biomed Pharmacother. 2025 Nov 19. pii: S0753-3322(25)01008-X. [Epub ahead of print]193 118814
    Mitochondrial stress bridge: Could muscle-derived extracellular vesicles be the missing link between sarcopenia, insulin resistance, and chemotherapy-induced cardiotoxicity?
    Okechukwu Paul-Chima Ugwu, Fabian C Ogenyi, Chinyere Nneoma Ugwu, Mariam Basajja, Michael Ben Okon.
      Sarcopenia is currently considered a systemic condition that goes beyond muscle atrophy to include multifunctional metabolic and cardiovascular dysfunction. The mediators between skeletal muscle loss and entire body insulin resistance and increased vulnerability to cardiotoxicity caused by chemotherapy are not clear. We hypothesise that mitochondrial-enriched, muscle-secreted extracellular vesicles (EVs) of mtDNA/mitoproteins, stress-regulated microRNAs (miR-1/133/206; miR-29 family), and ROS-modified damage-associated molecular patterns (DAMPs) are a mitochondrial stress bridge that secretes danger signals from sarcopenic muscle to the liver/adipose and heart. EV cargo mechanistically impairs insulin signaling (IRS-1 → PI3K-AKT → GLUT4) and cardiomyocyte pre-injury (loss of Δpsm, antioxidant repression, apoptosis), increasing the toxicity of doxorubicin. Should this framework be valid, it describes the clustering of sarcopenic patients with metabolic dysfunction and disproportional cardiotoxic incidents throughout cancer therapy and places circulating EV cargo as an indicator of outcomes and therapeutic interventions.
    Keywords:  Cardiotoxicity; Chemotherapy; Extracellular vesicles; Insulin resistance; Mitochondrial stress; Sarcopenia
    DOI:  https://doi.org/10.1016/j.biopha.2025.118814
  4. Exp Cell Res. 2025 Nov 13. pii: S0014-4827(25)00379-9. [Epub ahead of print] 114779
    LincRNA-p21 drives apoptosis and calcification of vascular smooth muscle cell via small extracellular vesicles under hyperphosphatemic conditions in chronic kidney disease.
    Jianbing Hao, Siyu Wang, Lirong Hao.
      Vascular calcification, a major contributor to cardiovascular morbidity, involves pathological osteogenic transdifferentiation of vascular smooth muscle cell (VSMC) under hyperphosphatemic conditions in chronic kidney disease. This study investigates the role of lincRNA-p21 and small extracellular vesicles in phosphate-induced mouse aortic smooth muscle cell (MASMC) calcification. Exposure to phosphate (2.6 mmol/L) triggered time-dependent calcification, characterized by enhanced calcium deposition, endoplasmic reticulum remodeling, and intracellular calcium accumulation (p<0.05 vs. 24/48-hour controls). Concurrently, the expression of osteogenic markers (BGP, OCN, and OPN) and lincRNA-p21 was significantly upregulated, whereas the expression of contractile phenotype-specific markers (SM22α, SM-MHC, and SM α-actin) was markedly down-regulated. This pattern of gene expression was correlated with MASMC osteogenic transdifferentiation. Small extracellular vesicles isolated from phosphate-treated MASMC exhibited elevated lincRNA-p21 levels (p<0.05) and induced calcification and apoptosis in recipient cells, suggesting small extracellular vesicles-mediated propagation of calcific signals. Functional studies demonstrated that lincRNA-p21 overexpression exacerbated calcification, apoptosis, and osteogenic marker expression, while its knockdown attenuated these effects (p<0.05). Time-course analyses revealed lincRNA-p21 dynamically regulates small extracellular vesicles secretion, calcium accumulation, and apoptotic pathways, acting as a molecular switch driving phosphate-induced calcification. These findings establish lincRNA-p21 as a critical mediator of MASMC calcification via small extracellular vesicles-dependent mechanisms, offering insights into therapeutic strategies for vascular calcification.
    Keywords:  chronic kidney disease; lincRNA-p21; small extracellular vesicles; vascular calcification; vascular smooth muscle cell
    DOI:  https://doi.org/10.1016/j.yexcr.2025.114779
  5. Sci Rep. 2025 Nov 21. 15(1): 41197
    Revealing the complexity of the epicardial secretome.
    Cláudia C Oliveira, José Córdoba, John R Pearson, Elizabeth Guruceaga, Ernesto Marín-Sedeño, María López-Moreno, Juan Antonio Guadix, Melissa García-Caballero, José M Pérez-Pomares, Adrián Ruiz-Villalba.
      The epicardium, an epithelial layer covering the heart, plays pivotal roles in embryonic heart development and responses to adult cardiac damage. Epicardial-secreted molecular agents are known to be involved in the regulation of these phenomena, but how this regulation occurs is poorly understood. In this study, we have investigated extracellular vesicle (EV) and extracellular matrix (ECM) components of the epicardial secretome using a continuous mouse embryonic epicardial-derived cell (EPIC) line. Epicardial-derived EVs were isolated using differential ultracentrifugation from EPIC cultured at 1% (EVs-H1%), 5% (EVs-H5%), and 21% oxygen (EVs-N). EVs protein content was determined by tandem mass tag (TMT) proteomic analysis. The results showed that epicardial-derived EVs cargo is sensitive to the oxygen level of parenteral cells, increasing their content on glycolytic proteins as oxygen level decreases. Moreover, hypoxic-derived EVs were found to both increase EPIC proliferation and affect the metabolism of Human Umbilical Vein Endothelial Cells (HUVECs). On the other hand, epicardial-derived extracellular matrix (EPIC-ECM) was characterized by submitting decellularized EPIC to shotgun proteomics and comparing it to decellularized perinatal hearts and Matrigel®. We found that EPIC-ECM composition closely resembles that of embryonic cardiac tissue. Although the structural and basement membrane-associated proteins of EPIC-ECM were similar to those found in Matrigel®, EPIC-ECM exhibited higher protein diversity and was a more potent inducer of HUVEC proliferation. This work represents the first comprehensive and systematic proteomic analysis of two important components of the epicardial-derived secretome. Our experiments reveal that the epicardium responds to hypoxia by secreting EVs capable of modifying the metabolic responses of surrounding cells. Furthermore, EPIC-ECM promotes endothelial cell proliferation. These findings demonstrate the significant signaling abilities of the epicardial secretome and its potential contribution to cardiac development, both consistent with reports of endothelial responses following cardiac ischemic damage.
    DOI:  https://doi.org/10.1038/s41598-025-24980-y
  6. Int J Biol Macromol. 2025 Nov 17. pii: S0141-8130(25)09650-3. [Epub ahead of print] 149093
    Development of heparinized agarose microspheres for the recovery of exosomes curing acute myocardial infarction.
    Shun-Hao Chuang, Yu-Xuan Guo, Kuan-Ju Chen, Yu-Ting Cheng, Shuian-Yin Lin, Fu-Chun Chiu, Cho-Kai Wu, Hsiao-Ying Chou, Chia-Ti Tsai, Hsieh-Chih Tsai.
      Exosomes carry biological molecules that are secreted by cells. They play a crucial role in intercellular communication and regulate physiological and pathological processes. This study develops heparinized agarose microspheres (HepCAMs) for affinity purification of EVs from a culture medium to address problems with low purity and scaling up. HepCAMs are used for exosome affinity purification using human lung adenocarcinoma alveolar epithelial cells (A549) and Human Umbilical Mesenchymal Stem Cells (HUMSCs) in a culture medium. The presence of purified exosomes is confirmed by measuring the particle size, concentration, morphology and surface markers. This method to isolate HepCAMs achieves twice the purity of exosomes at 8.9 × 107 particles/μg of protein than the SEC method. The bioactivity of HUMSCs exosomes that are purified using the HepCAMs is verified by measuring the internalization and wound healing of Human Umbilical Vein Endothelial Cells (HUVECs). For a myocardial infarction (MI) mouse model, HUMSCs exosome restores cardiac performance and blood flow recovery in myocardial infarction mice. These results show that the proposed method to isolate HepCAMs produces high-purity exosomes and the process is easily scaled up. The bioactivity of exosomes is confirmed and they are shown to improve heart function after ischemic injury in a MI mouse model.
    Keywords:  Affinity purification; Exosome; Heparin; Mesenchymal stem cell; Myocardial infarction
    DOI:  https://doi.org/10.1016/j.ijbiomac.2025.149093
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