08f47e7859f345f13e714dfceaa81d9b 290567.pdf 2041546c015e6e3885732a56fdb04e61a1fa5454 290567.pdf f3bfa759a631819b28e46910697506c9fc79affd5285647d323e9228a975ed97 290567.pdf Title: Extracellular Vesicles as Drivers of Immunoinflammation in Atherothrombosis Subject: Atherosclerotic cardiovascular disease is the leading cause of morbidity and mortality all over the world. Extracellular vesicles (EVs), small lipid-bilayer membrane vesicles released by most cellular types, exert pivotal and multifaceted roles in physiology and disease. Emerging evidence emphasizes the importance of EVs in intercellular communication processes with key effects on cell survival, endothelial homeostasis, inflammation, neoangiogenesis, and thrombosis. This review focuses on EVs as effective signaling molecules able to both derail vascular homeostasis and induce vascular dysfunction, inflammation, plaque progression, and thrombus formation as well as drive anti-inflammation, vascular repair, and atheroprotection. We provide a comprehensive and updated summary of the role of EVs in the development or regression of atherosclerotic lesions, highlighting the link between thrombosis and inflammation. Importantly, we also critically describe their potential clinical use as disease biomarkers or therapeutic agents in atherothrombosis. Keywords: atherothrombosis; atherosclerosis; extracellular vesicles; immunoinflammation; immunothrombosis; inflammation; microvesicles; thromboinflammation; thrombosis Author: Rosa Suades, Maria Francesca Greco, Teresa Padró and Lina Badimon Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Sun Jun 5 10:11:25 2022 CEST ModDate: Sun Jun 5 10:14:33 2022 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 30 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1016354 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- PAPUPC+VnURWPalladioL Type 1 Custom yes yes no 10 0 NKQSEA+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 MNFLZW+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 ODFJBN+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 SOZKOC+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 PFKOHU+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 46 0 BGYPLV+CMSY10 Type 1 Builtin yes yes no 68 0 JDWIZJ+EURM10 Type 1 Builtin yes yes no 72 0 HGHICA+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 113 0 HGHIDC+PalatinoLinotype TrueType WinAnsi yes yes no 116 0 HGHIDE+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 119 0 HGHPPI+TimesNewRoman CID TrueType Identity-H yes yes yes 122 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-04-17 02:47:31 CEST RepresentationInformation: 290567.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2024-04-16 11:13:00 CEST Size: 1016354 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 1039 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Extracellular Vesicles: Current State and Emerging Concepts Destination: section.2 Item: Title: EVs as Pathophysiological Drivers of Atherothrombosis Destination: section.3 Children: Item: Title: Atherogenesis Destination: subsection.3.1 Item: Title: Atheroinflammation Destination: subsection.3.2 Item: Title: Lesion Progression Destination: subsection.3.3 Children: Item: Title: Atherogenic Foam Cell Formation Destination: subsubsection.3.3.1 Item: Title: Vascular Smooth Muscle Cell Proliferation, Migration, and Phenotype Switching Destination: subsubsection.3.3.2 Item: Title: Intravascular Calcification Destination: subsubsection.3.3.3 Item: Title: Necrotic Core Destination: subsubsection.3.3.4 Item: Title: Advanced Lesion and Plaque Rupture Destination: subsection.3.4 Children: Item: Title: Arterial Neoangiogenesis and Intraplaque Hemorrhage Destination: subsubsection.3.4.1 Item: Title: Thrombus Formation after Rupture Destination: subsubsection.3.4.2 Item: Title: Extracellular Vesicles as Diagnostic and Prognostic Biomarkers Destination: section.4 Item: Title: Extracellular Vesicles as Therapeutic Tools Destination: section.5 Item: Title: Future Perspectives and Conclusions Destination: section.6 Item: Title: References Destination: section.6 Info: Title: Extracellular Vesicles as Drivers of Immunoinflammation in Atherothrombosis Author: Rosa Suades, Maria Francesca Greco, Teresa Padró and Lina Badimon Subject: Atherosclerotic cardiovascular disease is the leading cause of morbidity and mortality all over the world. Extracellular vesicles (EVs), small lipid-bilayer membrane vesicles released by most cellular types, exert pivotal and multifaceted roles in physiology and disease. Emerging evidence emphasizes the importance of EVs in intercellular communication processes with key effects on cell survival, endothelial homeostasis, inflammation, neoangiogenesis, and thrombosis. This review focuses on EVs as effective signaling molecules able to both derail vascular homeostasis and induce vascular dysfunction, inflammation, plaque progression, and thrombus formation as well as drive anti-inflammation, vascular repair, and atheroprotection. We provide a comprehensive and updated summary of the role of EVs in the development or regression of atherosclerotic lesions, highlighting the link between thrombosis and inflammation. Importantly, we also critically describe their potential clinical use as disease biomarkers or therapeutic agents in atherothrombosis. Keywords: atherothrombosis; atherosclerosis; extracellular vesicles; immunoinflammation; immunothrombosis; inflammation; microvesicles; thromboinflammation; thrombosis Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Sun Jun 05 10:11:25 CEST 2022 ModDate: Sun Jun 05 10:14:33 CEST 2022 ID: 0x293921ddb48254ef76796153e0597933, 0x293921ddb48254ef76796153e0597933 Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: MNFLZW+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 252 FontDescriptor: FontName: MNFLZW+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: BGYPLV+CMSY10 FontSubset: true FirstChar: 0 LastChar: 35 FontDescriptor: FontName: BGYPLV+CMSY10 Flags: Symbolic FontBBox: -29, -960, 1116, 775 FontFile: true Font: BaseFont: ODFJBN+URWPalladioL-Ital FontSubset: true FirstChar: 3 LastChar: 121 FontDescriptor: FontName: ODFJBN+URWPalladioL-Ital Flags: Symbolic 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Rect: 235, 458, 271, 468 Annotation: Subtype: Link Rect: 104, 423, 142, 433 Annotation: Subtype: Link Rect: 148, 423, 184, 433 Annotation: Subtype: Link Rect: 192, 389, 230, 399 Annotation: Subtype: Link Rect: 236, 389, 272, 399 Annotation: Subtype: Link Rect: 333, 353, 370, 364 Annotation: Subtype: Link Rect: 377, 353, 413, 364 Annotation: Subtype: Link Rect: 59, 320, 96, 330 Annotation: Subtype: Link Rect: 102, 320, 138, 330 Annotation: Subtype: Link Rect: 193, 284, 230, 295 Annotation: Subtype: Link Rect: 313, 262, 350, 272 Annotation: Subtype: Link Rect: 345, 238, 382, 249 Annotation: Subtype: Link Rect: 166, 205, 203, 215 Annotation: Subtype: Link Rect: 393, 169, 431, 180 Annotation: Subtype: Link Rect: 437, 169, 473, 180 Annotation: Subtype: Link Rect: 163, 136, 200, 146 Annotation: Subtype: Link Rect: 206, 136, 242, 146 Annotation: Subtype: Link Rect: 253, 101, 290, 111 Annotation: Subtype: Link Rect: 297, 101, 333, 111 Annotation: Subtype: Link Rect: 59, 67, 96, 77 Page: Sequence: 27 Annotations: Annotation: Subtype: Link Rect: 459, 710, 497, 721 Annotation: Subtype: Link Rect: 519, 687, 557, 698 Annotation: Subtype: Link Rect: 82, 653, 119, 664 Annotation: Subtype: Link Rect: 306, 618, 343, 629 Annotation: Subtype: Link Rect: 444, 595, 481, 606 Annotation: Subtype: Link Rect: 95, 561, 133, 571 Annotation: Subtype: Link Rect: 59, 527, 96, 537 Annotation: Subtype: Link Rect: 102, 527, 138, 537 Annotation: Subtype: Link Rect: 519, 503, 557, 514 Annotation: Subtype: Link Rect: 59, 492, 95, 502 Annotation: Subtype: Link Rect: 104, 458, 142, 468 Annotation: Subtype: Link Rect: 148, 458, 184, 468 Annotation: Subtype: Link Rect: 190, 423, 227, 433 Annotation: Subtype: Link Rect: 59, 389, 96, 399 Annotation: Subtype: Link Rect: 307, 365, 344, 376 Annotation: Subtype: Link Rect: 343, 330, 381, 341 Annotation: Subtype: Link Rect: 109, 297, 146, 307 Annotation: Subtype: Link Rect: 311, 261, 349, 272 Annotation: Subtype: Link Rect: 451, 239, 489, 249 Annotation: Subtype: Link Rect: 153, 216, 191, 226 Annotation: Subtype: Link Rect: 197, 216, 233, 226 Annotation: Subtype: Link Rect: 99, 182, 137, 192 Annotation: Subtype: Link Rect: 143, 182, 179, 192 Annotation: Subtype: Link Rect: 327, 158, 364, 169 Annotation: Subtype: Link Rect: 371, 158, 407, 169 Annotation: Subtype: Link Rect: 438, 123, 476, 134 Annotation: Subtype: Link Rect: 59, 90, 96, 100 Page: Sequence: 28 Annotations: Annotation: Subtype: Link Rect: 59, 711, 96, 721 Annotation: Subtype: Link Rect: 509, 687, 547, 698 Annotation: Subtype: Link Rect: 186, 665, 224, 675 Annotation: Subtype: Link Rect: 493, 629, 530, 640 Annotation: Subtype: Link Rect: 303, 606, 341, 617 Annotation: Subtype: Link Rect: 234, 583, 271, 594 Annotation: Subtype: Link Rect: 277, 583, 314, 594 Annotation: Subtype: Link Rect: 335, 561, 372, 571 Annotation: Subtype: Link Rect: 378, 561, 414, 571 Annotation: Subtype: Link Rect: 294, 526, 331, 537 Annotation: Subtype: Link Rect: 338, 526, 374, 537 Annotation: Subtype: Link Rect: 199, 492, 237, 502 Annotation: Subtype: Link Rect: 243, 492, 279, 502 Annotation: Subtype: Link Rect: 140, 458, 177, 468 Annotation: Subtype: Link Rect: 266, 434, 304, 445 Annotation: Subtype: Link Rect: 402, 399, 440, 410 Annotation: Subtype: Link Rect: 266, 365, 303, 376 Annotation: Subtype: Link Rect: 454, 342, 491, 353 Annotation: Subtype: Link Rect: 401, 319, 438, 330 Annotation: Subtype: Link Rect: 393, 296, 431, 307 Annotation: Subtype: Link Rect: 437, 296, 473, 307 Annotation: Subtype: Link Rect: 59, 262, 96, 272 Annotation: Subtype: Link Rect: 102, 262, 138, 272 Annotation: Subtype: Link Rect: 294, 238, 331, 249 Annotation: Subtype: Link Rect: 337, 238, 373, 249 Annotation: Subtype: Link Rect: 469, 204, 506, 215 Annotation: Subtype: Link Rect: 421, 181, 458, 192 Annotation: Subtype: Link Rect: 505, 158, 542, 169 Annotation: Subtype: Link Rect: 359, 123, 397, 134 Annotation: Subtype: Link Rect: 215, 89, 253, 100 Page: Sequence: 29 Annotations: Annotation: Subtype: Link Rect: 158, 711, 195, 721 Annotation: Subtype: Link Rect: 494, 687, 531, 698 Annotation: Subtype: Link Rect: 458, 664, 495, 675 Annotation: Subtype: Link Rect: 501, 664, 537, 675 Annotation: Subtype: Link Rect: 312, 629, 350, 640 Annotation: Subtype: Link Rect: 356, 629, 392, 640 Annotation: Subtype: Link Rect: 441, 595, 479, 606 Annotation: Subtype: Link Rect: 485, 595, 521, 606 Annotation: Subtype: Link Rect: 422, 572, 460, 583 Annotation: Subtype: Link Rect: 466, 572, 502, 583 Annotation: Subtype: Link Rect: 95, 550, 132, 560 Annotation: Subtype: Link Rect: 138, 550, 174, 560 Annotation: Subtype: Link Rect: 131, 527, 168, 537 Annotation: Subtype: Link Rect: 295, 504, 332, 514 Annotation: Subtype: Link Rect: 59, 469, 96, 479 Annotation: Subtype: Link Rect: 467, 445, 504, 456 Annotation: Subtype: Link Rect: 276, 422, 314, 433 Annotation: Subtype: Link Rect: 378, 388, 416, 399 Annotation: Subtype: Link Rect: 422, 388, 458, 399 Annotation: Subtype: Link Rect: 228, 354, 265, 364 Annotation: Subtype: Link Rect: 271, 354, 308, 364 Annotation: Subtype: Link Rect: 268, 331, 305, 341 Annotation: Subtype: Link Rect: 311, 331, 347, 341 Annotation: Subtype: Link Rect: 170, 308, 207, 318 Annotation: Subtype: Link Rect: 478, 273, 515, 284 Annotation: Subtype: Link Rect: 521, 273, 557, 284 Annotation: Subtype: Link Rect: 59, 239, 96, 249 Annotation: Subtype: Link Rect: 102, 239, 138, 249 Annotation: Subtype: Link Rect: 59, 205, 96, 215 Annotation: Subtype: Link Rect: 424, 181, 462, 192 Annotation: Subtype: Link Rect: 314, 146, 352, 157 Annotation: Subtype: Link Rect: 191, 113, 229, 123 Annotation: Subtype: Link Rect: 291, 89, 329, 100 Annotation: Subtype: Link Rect: 335, 89, 371, 100 Annotation: Subtype: Link Rect: 248, 67, 285, 77 Annotation: Subtype: Link Rect: 292, 67, 328, 77 Page: Sequence: 30 Annotations: Annotation: Subtype: Link Rect: 334, 722, 372, 733 Annotation: Subtype: Link Rect: 453, 710, 491, 721 Annotation: Subtype: Link Rect: 497, 710, 533, 721 Annotation: Subtype: Link Rect: 208, 676, 246, 687 Annotation: Subtype: Link Rect: 252, 676, 288, 687 Annotation: Subtype: Link Rect: 95, 642, 133, 652 Annotation: Subtype: Link Rect: 139, 642, 175, 652 Annotation: Subtype: Link Rect: 204, 607, 242, 617 Annotation: Subtype: Link Rect: 59, 573, 96, 583 Annotation: Subtype: Link Rect: 501, 537, 539, 548 Annotation: Subtype: Link Rect: 100, 504, 138, 514 Annotation: Subtype: Link Rect: 520, 480, 557, 491 Annotation: Subtype: Link Rect: 59, 446, 96, 456 Annotation: Subtype: Link Rect: 102, 446, 138, 456 Annotation: Subtype: Link Rect: 250, 411, 287, 422 Annotation: Subtype: Link Rect: 294, 411, 330, 422 Annotation: Subtype: Link Rect: 519, 388, 557, 399 Annotation: Subtype: Link Rect: 59, 377, 95, 387 Annotation: Subtype: Link Rect: 95, 354, 133, 364 Annotation: Subtype: Link Rect: 139, 354, 175, 364 Checksum: 75fb757f Type: CRC32 Checksum: 08f47e7859f345f13e714dfceaa81d9b Type: MD5 Checksum: 2041546c015e6e3885732a56fdb04e61a1fa5454 Type: SHA-1 Checksum: f3bfa759a631819b28e46910697506c9fc79affd5285647d323e9228a975ed97 Type: SHA-256