26c58f897d64f9647cc771130b9db407 296608.pdf fdb09c9c70bf5c75ee8a82997f82f24bb1bd76d2 296608.pdf 5c1346cffd2719b4fd1a9348e9570dc46af5c8e910ae2e12a3e1f2e2f65c6431 296608.pdf Title: PDE4 Phosphodiesterases in Cardiovascular Diseases: Key Pathophysiological Players and Potential Therapeutic Targets Subject: 3',5'-cyclic adenosine monophosphate (cAMP) is a second messenger critically involved in the control of a myriad of processes with significant implications for vascular and cardiac cell function. The temporal and spatial compartmentalization of cAMP is governed by the activity of phosphodiesterases (PDEs), a superfamily of enzymes responsible for the hydrolysis of cyclic nucleotides. Through the fine-tuning of cAMP signaling, PDE4 enzymes could play an important role in cardiac hypertrophy and arrhythmogenesis, while it decisively influences vascular homeostasis through the control of vascular smooth muscle cell proliferation, migration, differentiation and contraction, as well as regulating endothelial permeability, angiogenesis, monocyte/macrophage activation and cardiomyocyte function. This review summarizes the current knowledge and recent advances in understanding the contribution of the PDE4 subfamily to cardiovascular function and underscores the intricate challenges associated with targeting PDE4 enzymes as a therapeutic strategy for the management of cardiovascular diseases. Keywords: PDE4; cardiovascular diseases; therapy Author: Lídia Puertas-Umbert, Judith Alonso, Leif Hove-Madsen, José Martínez-González and Cristina Rodríguez Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Fri Dec 1 06:32:22 2023 CET ModDate: Fri Dec 1 06:35:34 2023 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 19 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1319744 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- ATERRI+VnURWPalladioL Type 1 Custom yes yes no 10 0 FZQUMM+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 IIDPAI+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 ZMTZBC+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 SAUAIP+CMSY10 Type 1 Builtin yes yes no 28 0 IOJCNK+VnURWPalladioL-Bold Type 1 Custom yes yes no 32 0 IRWHZX+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 50 0 CKUPDE+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 53 0 PalatinoLinotype-Bold TrueType WinAnsi no no no 77 0 PalatinoLinotype-Roman TrueType WinAnsi no no no 80 0 PalatinoLinotype-Italic TrueType WinAnsi no no no 83 0 PalatinoLinotype-Bold TrueType WinAnsi no no no 93 0 PalatinoLinotype-Roman TrueType WinAnsi no no no 96 0 PalatinoLinotype-Italic TrueType WinAnsi no no no 99 0 JDWIZJ+EURM10 Type 1 Builtin yes yes no 109 0 PalatinoLinotype-Bold TrueType WinAnsi no no no 118 0 PalatinoLinotype-Roman TrueType WinAnsi no no no 121 0 PalatinoLinotype-Italic TrueType WinAnsi no no no 124 0 FNTSBS+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 127 0 IOLAWT+PazoMath-Italic Type 1 Builtin yes yes no 147 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-07-18 02:37:00 CEST RepresentationInformation: 296608.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2024-07-17 13:31:28 CEST Size: 1319744 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 546 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: The PDE4 Enzyme Family: Structure, Classification and Compartmentalization of cAMP Destination: section.2 Item: Title: Role of PDE4 Enzymes in Vascular Cell Function Destination: section.3 Children: Item: Title: Role of PDE4 Enzymes in the Endothelium Destination: subsection.3.1 Item: Title: PDE4 Activity in Vascular Smooth Muscle Cells (VSMCs) Destination: subsection.3.2 Children: Item: Title: Contribution of PDE4 to the Control of VSMC Proliferation and Migration Destination: subsubsection.3.2.1 Item: Title: VSMC Phenotypic Switch and PDE4 Activity Destination: subsubsection.3.2.2 Item: Title: Role of PDE4 Activity on the Control of Vascular Tone: Impact on Hypertension Destination: section.4 Item: Title: Impact of PDE4 on Vascular Aneurysm Development Destination: section.5 Item: Title: PDE4 in Cardiac Diseases Destination: section.6 Item: Title: PDE4 Inhibitors: New Approaches Destination: section.7 Item: Title: Conclusions and Future Directions Destination: section.8 Item: Title: References Destination: section.9 Info: Title: PDE4 Phosphodiesterases in Cardiovascular Diseases: Key Pathophysiological Players and Potential Therapeutic Targets Author: Lídia Puertas-Umbert, Judith Alonso, Leif Hove-Madsen, José Martínez-González and Cristina Rodríguez Subject: 3',5'-cyclic adenosine monophosphate (cAMP) is a second messenger critically involved in the control of a myriad of processes with significant implications for vascular and cardiac cell function. The temporal and spatial compartmentalization of cAMP is governed by the activity of phosphodiesterases (PDEs), a superfamily of enzymes responsible for the hydrolysis of cyclic nucleotides. Through the fine-tuning of cAMP signaling, PDE4 enzymes could play an important role in cardiac hypertrophy and arrhythmogenesis, while it decisively influences vascular homeostasis through the control of vascular smooth muscle cell proliferation, migration, differentiation and contraction, as well as regulating endothelial permeability, angiogenesis, monocyte/macrophage activation and cardiomyocyte function. This review summarizes the current knowledge and recent advances in understanding the contribution of the PDE4 subfamily to cardiovascular function and underscores the intricate challenges associated with targeting PDE4 enzymes as a therapeutic strategy for the management of cardiovascular diseases. 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