Lactadherin Deficiency Leads to Apoptotic Cell Accumulation and Accelerated Atherosclerosis in Mice

Inflammation, Atherosclerosis, and Coronary Artery Disease

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Atherosclerosis

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Cytokines in Atherosclerosis: Pathogenic and Regulatory Pathways

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A blast from the past: clearance of apoptotic cells regulates immune responses

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Prevalence and Correlates of Accelerated Atherosclerosis in Systemic Lupus Erythematosus

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Identification of a factor that links apoptotic cells to phagocytes

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The Induction of Tolerance by Dendritic Cells That Have Captured Apoptotic Cells

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Natural regulatory T cells control the development of atherosclerosis in mice

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Autoimmune Disease and Impaired Uptake of Apoptotic Cells in MFG-E8-Deficient Mice

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Apoptotic Cells Induce Migration of Phagocytes via Caspase-3-Mediated Release of a Lipid Attraction Signal

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Heterogeneity of atherosclerotic plaque macrophage origin, phenotype and functions: Implications for treatment

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Phagocytosis by macrophages and endothelial cells inhibits procoagulant and fibrinolytic activity of acute promyelocytic leukemia cells

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Cell surface-expressed phosphatidylserine as therapeutic target to enhance phagocytosis of apoptotic cells

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MFG-E8 mediates arterial aging by promoting the proinflammatory phenotype of vascular smooth muscle cells

Chiang, H., Chu, P., & Lee, T. (2019) · Journal of Biomedical Science · doi:10.1186/s12929-019-0559-0 · Cited by 49

Neutrophils in atherosclerosis

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Milk Fat Globule Epidermal Growth Factor VIII Signaling in Arterial Wall Remodeling

Wang, M., Wang, H. H., & Lakatta, E. G. (2013) · Current Vascular Pharmacology · doi:10.2174/1570161111311050014 · Cited by 49

Adoptive transfer of CX3CR1 transduced-T regulatory cells improves homing to the atherosclerotic plaques and dampens atherosclerosis progression

Bonacina, F., Martini, E., Svecla, M., Nour, J., Cremonesi, M., Beretta, G., Moregola, A., Pellegatta, F., Zampoleri, V., Catapano, A. L., et al. (2020) · Cardiovascular Research · doi:10.1093/cvr/cvaa264 · Cited by 49

Hematopoietic Interferon Regulatory Factor 8-Deficiency Accelerates Atherosclerosis in Mice

Döring, Y., Soehnlein, O., Drechsler, M. D., Shagdarsuren, E., Chaudhari, S. M., Meiler, S. U., Hartwig, H., Hristov, M., Koenen, R. R., Hieronymus, T., et al. (2012) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.111.236539 · Cited by 48

Lactadherin: An unappreciated haemostasis regulator and potential therapeutic agent

Kamińska, A., Enguita, F. J., & Stępień, E. Ł. (2017) · Vascular Pharmacology · doi:10.1016/j.vph.2017.11.006 · Cited by 47

MFGE8 attenuates Ang-II-induced atrial fibrosis and vulnerability to atrial fibrillation through inhibition of TGF-β1/Smad2/3 pathway

Ge, Z., Chen, Y., Wang, B., Zhang, X., Yan, Y., Zhou, L., Zhang, Y., & Xie, Y. (2020) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2020.01.001 · Cited by 47

Proinflammatory Arterial Stiffness Syndrome: A Signature of Large Arterial Aging

Wang, M., Monticone, R. E., & McGraw, K. R. (2018) · Journal of Vascular Research · doi:10.1159/000490244 · Cited by 52

Roles and mechanisms of MFG-E8 in vascular aging-related diseases

Ni, Y., Zhan, J., & Liu, Y. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101176 · Cited by 45

Endothelial Cell–derived Microparticles Loaded with Iron Oxide Nanoparticles: Feasibility of MR Imaging Monitoring in Mice

Faraj, A. A., Gazeau, F., Wilhelm, C., Devue, C., Guérin, C. L., Péchoux, C., Paradis, V., Clémеnt, O., Boulanger, C. M., & Rautou, P. (2012) · Radiology · doi:10.1148/radiol.11111329 · Cited by 44

NMR solution structure of C2 domain of MFG-E8 and insights into its molecular recognition with phosphatidylserine

Ye, H., Li, B., Vivekanandan, S., Choi, B.-H., Yu, L., Harikishore, A., Chakraborty, G., Baek, K., & Yoon, H. S. (2012) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2012.12.009 · Cited by 44

The Dendritic Cell Receptor DNGR-1 Promotes the Development of Atherosclerosis in Mice

Haddad, Y., Lahoute, C., Clément, M., Laurans, L., Metghalchi, S., Zeboudj, L., Giraud, A., Loyer, X., Vandestienne, M., Wain‐Hobson, J., et al. (2017) · Circulation Research · doi:10.1161/circresaha.117.310960 · Cited by 44

Metabolic Consequences of Efferocytosis and Its Impact on Atherosclerosis

Yurdagul, A. (2021) · Immunometabolism · doi:10.20900/immunometab20210017 · Cited by 41

Allograft inflammatory factor-1 supports macrophage survival and efferocytosis and limits necrosis in atherosclerotic plaques

Egaña-Gorroño, L., Chinnasamy, P., Casimiro, I., Almonte, V. M., Parikh, D., Oliveira‐Paula, G. H., Jayakumar, S., Law, C., Riascos‐Bernal, D. F., & Sibinga, N. E. S. (2019) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2019.07.022 · Cited by 41

The roles of a novel anti-inflammatory factor, milk fat globule-epidermal growth factor 8, in patients with coronary atherosclerotic heart disease

Dai, W., Li, Y., Lv, Y.-N., Wei, C., & Zheng, H. (2014) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2014.01.013 · Cited by 41

Milk Fat Globule–Epidermal Growth Factor–Factor 8 Improves Hepatic Steatosis and Inflammation

Zhang, L., Tian, R., Yao, X., Zhang, X., Zhang, P., Huang, Y., She, Z., Li, H., Ji, Y., & Cai, J. (2020) · Hepatology · doi:10.1002/hep.31277 · Cited by 40

Dead cell and debris clearance in the atherosclerotic plaque: Mechanisms and therapeutic opportunities to promote inflammation resolution

Dhawan, U. K., Singhal, A., & Subramanian, M. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2021.105699 · Cited by 41

Cardiovascular disease in systemic lupus erythematosus is associated with increased levels of biomarkers reflecting receptor-activated apoptosis

Wigren, M., Svenungsson, E., Mattisson, I. Y., Gustafsson, J. T., Gunnarsson, I., Zickert, A., Elvin, K., Jensen‐Urstad, K., Bengtsson, A. A., Gullstrand, B., et al. (2018) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2018.01.022 · Cited by 38

Efferocytosis in multisystem diseases (Review)

Zhang, Y., Wang, Y., Ding, J., & Liu, P. (2021) · Molecular Medicine Reports · doi:10.3892/mmr.2021.12529 · Cited by 38

The amelioration of phagocytic ability in microglial cells by curcumin through the inhibition of EMF-induced pro-inflammatory responses

He, G., Liu, Y., Li, M., Chen, C., Gao, P., Yu, Z., & Yang, X. (2014) · Journal of Neuroinflammation · doi:10.1186/1742-2094-11-49 · Cited by 36

Atheroprotector role of the spleen based on the teaching of Avicenna (Ibn Sina)

Emtiazy, M., Choopani, R., Khodadoost, M., Tansaz, M., & Nazem, E. (2012) · International Journal of Cardiology · doi:10.1016/j.ijcard.2012.06.020 · Cited by 34

Novel drug discovery strategies for atherosclerosis that target necrosis and necroptosis

Coornaert, I., Hofmans, S., Devisscher, L., Augustyns, K., der Veken, P. V., Meyer, G. R. Y. D., & Martinet, W. (2018) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2018.1457644 · Cited by 35

Erythrophagocytosis by angiogenic endothelial cells is enhanced by loss of erythrocyte deformability

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The role of nucleotides in apoptotic cell clearance: implications for disease pathogenesis

Chekeni, F. B., & Ravichandran, K. S. (2010) · Journal of Molecular Medicine · doi:10.1007/s00109-010-0673-7 · Cited by 34

Guanxinkang Decoction Attenuates the Inflammation in Atherosclerosis by Regulating Efferocytosis and MAPKs Signaling Pathway in LDLR−/− Mice and RAW264.7 Cells

Zhang, Y., Ding, J., Wang, Y., Feng, X., Du, M., & Liu, P. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.731769 · Cited by 33

Localized amyloids important in diseases outside the brain – lessons from the islets of Langerhans and the thoracic aorta

Westermark, G. T., & Westermark, P. (2011) · FEBS Journal · doi:10.1111/j.1742-4658.2011.08298.x · Cited by 33

The glycoproteins EDIL3 and MFGE8 regulate vesicle-mediated eggshell calcification in a new model for avian biomineralization

Stapane, L., Roy, N. L., Hincke, M. T., & Gautron, J. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.009799 · Cited by 32

Innate differences and colostrum-induced alterations of jejunal mucosal proteins in piglets with intra-uterine growth restriction

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Contrasting Inflammation Resolution during Atherosclerosis and Post Myocardial Infarction at the Level of Monocyte/Macrophage Phagocytic Clearance

Thorp, E. B. (2012) · Frontiers in Immunology · doi:10.3389/fimmu.2012.00039 · Cited by 31

Identification of major milk fat globule membrane proteins from pony mare milk highlights the molecular diversity of lactadherin across species

Cebo, C., Rebours, E., Henry, C., Makhzami, S., Cosette, P., & Martin, P. (2012) · Journal of Dairy Science · doi:10.3168/jds.2011-4455 · Cited by 31

Regulation of MFGE8 by the intergenic coronary artery disease locus on 15q26.1

Soubeyrand, S., Nikpay, M., Turner, A. W., Dang, A.-T., Herfkens, M., Lau, P., & McPherson, R. (2019) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2019.02.012 · Cited by 30

Signalling from dead cells drives inflammation and vessel remodelling

Bennett, M. R., Yu, H., & Clarke, M. C. H. (2012) · Vascular Pharmacology · doi:10.1016/j.vph.2012.01.006 · Cited by 29

Telomerase Mediates Lymphocyte Proliferation but Not the Atherosclerosis-Suppressive Potential of Regulatory T-Cells

Richardson, G. D., Sage, A., Bennaceur, K., Zhrany, N. A., Coelho‐Lima, J., Dookun, E., Draganova, L., Saretzki, G. C., Breault, D. T., Mallat, Z., et al. (2018) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.117.309940 · Cited by 29

Del-etion of Microvesicles From the Circulation

Rautou, P., & Mackman, N. (2012) · Circulation · doi:10.1161/circulationaha.112.094920 · Cited by 29

FADD, Caspase-3, and Caspase-8 and Incidence of Coronary Events

Xue, L., Borné, Y., Mattisson, I. Y., Wigren, M., Melander, O., Ohro-Melander, M., Bengtsson, E., Fredrikson, G. N., Nilsson, J. Å., & Engström, G. (2017) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.117.308995 · Cited by 28

Airway tissue factor-dependent coagulation activity in response to sulfur mustard analog 2-chloroethyl ethyl sulfide

Rancourt, R. C., Veress, L. A., Guo, X., Jones, T. N., Hendry‐Hofer, T. B., & White, C. W. (2011) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00306.2010 · Cited by 27

MFG-E8 promotes osteogenic transdifferentiation of smooth muscle cells and vascular calcification by regulating TGF-β1 signaling

Chiang, H., Chu, P., Chen, S., & Lee, T. (2022) · Communications Biology · doi:10.1038/s42003-022-03313-z · Cited by 26

Distinct roles for complement in glomerulonephritis and atherosclerosis revealed in mice with a combination of lupus and hyperlipidemia

Lewis, M., Malik, T. H., Fossati‐Jimack, L., Carassiti, D., Cook, H. T., Haskard, D. O., & Botto, M. (2012) · Arthritis & Rheumatism · doi:10.1002/art.34451 · Cited by 26

Transglutaminase 2 Deficiency Decreases Plaque Fibrosis and Increases Plaque Inflammation in Apolipoprotein-E-Deficient Mice

Herck, J. L., Schrijvers, D. M., Meyer, G. R. Y. D., Martinet, W., Hove, C. E. V., Bult, H., Vrints, C. J., & Herman, A. G. (2009) · Journal of Vascular Research · doi:10.1159/000255966 · Cited by 26

Roles of Milk Fat Globule-Epidermal Growth Factor 8 in Intestinal Inflammation

Kusunoki, R., Ishihara, S., Aziz, M., Oka, A., Tada, Y., & Kinoshita, Y. (2012) · Digestion · doi:10.1159/000334679 · Cited by 26

Cause or Consequence

Clarke, M. C. H., & Bennett, M. R. (2008) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.108.179903 · Cited by 26

Phytochemical-mediated efferocytosis and autophagy in inflammation control

Vafadar, A., Tajbakhsh, A., Hosseinpour-Soleimani, F., Savardshtaki, A., & Hashempur, M. H. (2024) · Cell Death Discovery · doi:10.1038/s41420-024-02254-2 · Cited by 27

The mechanisms of vascular aging

Wang, S., Hu, S., & Mao, Y. (2021) · Aging Medicine · doi:10.1002/agm2.12151 · Cited by 25

Ferroptosis: a potential target for the treatment of atherosclerosis

Li, C., Liu, R., Xiong, Z., Bao, X., Liang, S., Zeng, H., Wei, J. J., Gong, Q., Liu, L., & Guo, J. (2024) · Acta Biochimica et Biophysica Sinica · doi:10.3724/abbs.2024016 · Cited by 25

PPARα activation differently affects microparticle content in atherosclerotic lesions and liver of a mouse model of atherosclerosis and NASH

Baron, M., Leroyer, A. S., Majd, Z., Lalloyer, F., Vallez, E., Bantubungi, K., Chinetti, G., Delerive, P., Boulanger, C. M., Staels, B., et al. (2011) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2011.03.009 · Cited by 25

The angiogenic factor Del1 prevents apoptosis of endothelial cells through integrin binding

Wang, Z., Kundu, R. K., Longaker, M. T., Quertermous, T., & Yang, G. P. (2011) · Surgery · doi:10.1016/j.surg.2011.07.013 · Cited by 23

Role of milk fat globule-epidermal growth factor 8 in colonic inflammation and carcinogenesis

Kusunoki, R., Ishihara, S., Tada, Y., Oka, A., Sonoyama, H., Fukuba, N., Oshima, N., Moriyama, I., Yuki, T., Kawashima, K., et al. (2015) · Journal of Gastroenterology · doi:10.1007/s00535-014-1036-x · Cited by 23

Bring out your dead

Hume, D. A. (2007) · Nature Immunology · doi:10.1038/ni0108-12 · Cited by 23

Immune system and atherosclerosis: Hostile or friendly relationship

Razeghian‐Jahromi, I., Akhormeh, A. K., Razmkhah, M., & Zibaeenezhad, M. J. (2022) · International Journal of Immunopathology and Pharmacology · doi:10.1177/03946320221092188 · Cited by 22

Oxidized Low-Density Lipoprotein–Induced Apoptotic Dendritic Cells as a Novel Therapy for Atherosclerosis

Frodermann, V., van Puijvelde, G. H. M., Wierts, L., Lagraauw, H. M., Foks, A. C., van Santbrink, P. J., Bot, I., Kuiper, J., & de Jager, S. C. A. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1401843 · Cited by 22

The association between plasma caspase-3, atherosclerosis, and vascular function in the Dallas Heart Study

Matulevicius, S. A., Rohatgi, A. K., Khera, A., Das, S. R., Owens, W. A., Ayers, C. R., Timaran, C. H., Rosero, E. B., Drazner, M. H., Peshock, R. M., et al. (2008) · APOPTOSIS · doi:10.1007/s10495-008-0254-1 · Cited by 22

The dynamic lives of macrophage and dendritic cell subsets in atherosclerosis

Taghavie-Moghadam, P. L., Butcher, M. J., & Galkina, E. (2014) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12392 · Cited by 21

Macrophage mediators and mechanisms in cardiovascular disease

Schelemei, P., Wagner, E., Picard, F. S. R., & Winkels, H. (2024) · The FASEB Journal · doi:10.1096/fj.202302001r · Cited by 23

Hematopoietic G‐protein‐coupled receptor kinase 2 deficiency decreases atherosclerotic lesion formation in LDL receptor‐knockout mice

Otten, J. J. T., de Jager, S. C. A., Kavelaars, A., Seijkens, T. T. P., Bot, I., Wijnands, E., Beckers, L., Westra, M. M., Bot, M., Busch, M. H., et al. (2012) · The FASEB Journal · doi:10.1096/fj.12-205351 · Cited by 21

2021 Jeffrey M. Hoeg Award Lecture: Defining the Role of Efferocytosis in Cardiovascular Disease: A Focus on the CD47 (Cluster of Differentiation 47) Axis

Jarr, K.-U., Kojima, Y., Weissman, I. L., & Leeper, N. J. (2022) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.122.317049 · Cited by 21

VE-cadherin cleavage by ovarian cancer microparticles induces β-catenin phosphorylation in endothelial cells

Al-Thawadi, H., Abu-Kaoud, N., Farsi, H. A., Hoarau-Véchot, J., Rafii, S., Rafii, A., & Pasquier, J. (2015) · Oncotarget · doi:10.18632/oncotarget.6677 · Cited by 20

Deficiency in milk fat globule-epidermal growth factor-factor 8 exacerbates organ injury and mortality in neonatal sepsis

Hansen, L. W., Khader, A., Yang, W.-L., Jacob, A., Chen, T., Nicastro, J. M., Coppa, G. F., Prince, J. M., & Wang, P. (2016) · Journal of Pediatric Surgery · doi:10.1016/j.jpedsurg.2016.12.022 · Cited by 20

Inflammatory and Autoimmune Reactions in Atherosclerosis and Vaccine Design Informatics

Jan, M., Meng, S., Chen, N. C., Mai, J., Wang, H., & Yang, X. (2010) · BioMed Research International · doi:10.1155/2010/459798 · Cited by 19

Molecular Imaging to Identify the Vulnerable Plaque—From Basic Research to Clinical Practice

Kusters, D. H. M., Tegtmeier, J., Schurgers, L. J., & Reutelingsperger, C. P. M. (2012) · Molecular Imaging and Biology · doi:10.1007/s11307-012-0586-7 · Cited by 20

MFG-E8, a clearance glycoprotein of apoptotic cells, as a new marker of disease severity in chronic obstructive pulmonary disease

Zhang, S., Xie, J., Su, B., Li, J. L., Hu, N., Chen, J., Luo, G., & Cui, T. (2015) · Brazilian Journal of Medical and Biological Research · doi:10.1590/1414-431x20154730 · Cited by 19

Autoregulation of insulin receptor signaling through MFGE8 and the αvβ5 integrin

Datta, R., Lizama, C. O., Soltani, A. K., McKleroy, W., Podolsky, M. J., Yang, C. D., Huynh, T. L., Cautivo, K. M., Wang, B., Koliwad, S. K., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2102171118 · Cited by 18

Inframe insertion and splice site variants in MFGE8 associate with protection against coronary atherosclerosis

Ruotsalainen, S., Surakka, I. L., Mars, N., Karjalainen, J. M., Kurki, M., Kanai, M., Krebs, K., Graham, S. E., Mishra, P. P., Mishra, B. H., et al. (2022) · Communications Biology · doi:10.1038/s42003-022-03552-0 · Cited by 21

Expression and characterization of recombinant human milk fat globule-EGF factor VIII

Wang, P. (2011) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2011.782 · Cited by 17

Extracellular vesicles in venous thromboembolism and pulmonary hypertension

Zhang, J., Hu, X., Wang, T., Xiao, R., Zhu, L., Ruiz, M., Dupuis, J., & Hu, Q. (2023) · Journal of Nanobiotechnology · doi:10.1186/s12951-023-02216-3 · Cited by 16

Milk fat globule epidermal growth factor 8 inhibits periodontitis in non‐human primates and its gingival crevicular fluid levels can differentiate periodontal health from disease in humans

Kajikawa, T., Meshikhes, F., Maekawa, T., Hajishengallis, E., Hosur, K. B., Abe, T., MOSS, K. L., Chavakis, T., & Hajishengallis, G. (2017) · Journal Of Clinical Periodontology · doi:10.1111/jcpe.12707 · Cited by 16

Heterogeneity of Macrophages in Atherosclerosis

Stremmel, C., Stark, K., & Schulz, C. (2019) · Thrombosis and Haemostasis · doi:10.1055/s-0039-1692665 · Cited by 16

Absence of the MFG‐E8 gene prevents hypoxia‐induced pulmonary hypertension in mice

Wang, J., Wu, J., Zhu, X., Chen, J., Zhao, J., Xu, Y., & Xie, J. (2020) · Journal of Cellular Physiology · doi:10.1002/jcp.29885 · Cited by 15

Reduced serum milk fat globule-epidermal growth factor 8 (MFG-E8) concentrations are associated with an increased risk of microvascular complications in patients with type 2 diabetes

Sun, G., Liu, J., Xia, G., Zhang, L.-J., Li, Y., Zhou, Z., Lv, Y., Wei, S., Liu, J., & Quan, J. (2017) · Clinica Chimica Acta · doi:10.1016/j.cca.2017.01.013 · Cited by 15

Anti-inflammatory action of apoptotic cells in patients with acute coronary syndromes

Ferri, L., Maugeri, N., Rovere, P. Q., Calabrese, A., Ammirati, E., Cianflone, D., Maseri, A., & Manfredi, A. A. (2009) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2008.12.042 · Cited by 14

Deletion of MFGE8 Inhibits Neointima Formation upon Arterial Damage

Viola, J. R., Lemnitzer, P., Paulin, N., Drechsler, M. D., Nazari-Jahantigh, M., Maas, S. L., de Jong, R., Winter, J., Schober, A., Weber, C., et al. (2018) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1649522 · Cited by 13

Mechanism of efferocytosis in atherosclerosis

Shu, L.-X., Cao, L.-L., Guo, X., Wang, Z., & Wang, S. (2024) · Journal of Molecular Medicine · doi:10.1007/s00109-024-02439-3 · Cited by 16

Mouse models of atherosclerosis

Potteaux, S., Ait‐Oufella, H., & Mallat, Z. (2007) · Drug Discovery Today Disease Models · doi:10.1016/j.ddmod.2007.11.005 · Cited by 12

HDL, PTX3, and Vascular Protection

Mallat, Z., & Tedgui, A. (2008) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.108.163204 · Cited by 12

MFG‐E8 Regulates Vascular Smooth Muscle Cell Migration Through Dose‐Dependent Mediation of Actin Polymerization

Chiang, H., Chu, P., Chen, S., & Lee, T. (2021) · Journal of the American Heart Association · doi:10.1161/jaha.121.020870 · Cited by 11

MFGE8 does not orchestrate clearance of apoptotic neurons in a mouse model of Parkinson's disease

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Defective macrophage efferocytosis in advanced atherosclerotic plaque and mitochondrial therapy

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