cGMP Signaling and Vascular Smooth Muscle Cell Plasticity
Cyclic GMP regulates multiple cell types and functions of the cardiovascular system. This review summarizes the effects of cGMP on the growth and survival of vascular smooth muscle cells (VSMCs), which display remarkable phenotypic plasticity during the development of vascular diseases, such as athe...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2018-04-01
|
| Series: | Journal of Cardiovascular Development and Disease |
| Subjects: | |
| Online Access: | http://www.mdpi.com/2308-3425/5/2/20 |
| _version_ | 1818541632700547072 |
|---|---|
| author | Moritz Lehners Hyazinth Dobrowinski Susanne Feil Robert Feil |
| author_facet | Moritz Lehners Hyazinth Dobrowinski Susanne Feil Robert Feil |
| author_sort | Moritz Lehners |
| collection | DOAJ |
| description | Cyclic GMP regulates multiple cell types and functions of the cardiovascular system. This review summarizes the effects of cGMP on the growth and survival of vascular smooth muscle cells (VSMCs), which display remarkable phenotypic plasticity during the development of vascular diseases, such as atherosclerosis. Recent studies have shown that VSMCs contribute to the development of atherosclerotic plaques by clonal expansion and transdifferentiation to macrophage-like cells. VSMCs express a variety of cGMP generators and effectors, including NO-sensitive guanylyl cyclase (NO-GC) and cGMP-dependent protein kinase type I (cGKI), respectively. According to the traditional view, cGMP inhibits VSMC proliferation, but this concept has been challenged by recent findings supporting a stimulatory effect of the NO-cGMP-cGKI axis on VSMC growth. Here, we summarize the relevant studies with a focus on VSMC growth regulation by the NO-cGMP-cGKI pathway in cultured VSMCs and mouse models of atherosclerosis, restenosis, and angiogenesis. We discuss potential reasons for inconsistent results, such as the use of genetic versus pharmacological approaches and primary versus subcultured cells. We also explore how modern methods for cGMP imaging and cell tracking could help to improve our understanding of cGMP’s role in vascular plasticity. We present a revised model proposing that cGMP promotes phenotypic switching of contractile VSMCs to VSMC-derived plaque cells in atherosclerotic lesions. Regulation of vascular remodeling by cGMP is not only an interesting new therapeutic strategy, but could also result in side effects of clinically used cGMP-elevating drugs. |
| first_indexed | 2024-12-11T22:11:48Z |
| format | Article |
| id | doaj.art-3696f06879b043b4975094013d030e29 |
| institution | Directory Open Access Journal |
| issn | 2308-3425 |
| language | English |
| last_indexed | 2024-12-11T22:11:48Z |
| publishDate | 2018-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Cardiovascular Development and Disease |
| spelling | doaj.art-3696f06879b043b4975094013d030e292022-12-22T00:48:45ZengMDPI AGJournal of Cardiovascular Development and Disease2308-34252018-04-01522010.3390/jcdd5020020jcdd5020020cGMP Signaling and Vascular Smooth Muscle Cell PlasticityMoritz Lehners0Hyazinth Dobrowinski1Susanne Feil2Robert Feil3Interfaculty Institute of Biochemistry, University of Tübingen, 72076 Tübingen, GermanyInterfaculty Institute of Biochemistry, University of Tübingen, 72076 Tübingen, GermanyInterfaculty Institute of Biochemistry, University of Tübingen, 72076 Tübingen, GermanyInterfaculty Institute of Biochemistry, University of Tübingen, 72076 Tübingen, GermanyCyclic GMP regulates multiple cell types and functions of the cardiovascular system. This review summarizes the effects of cGMP on the growth and survival of vascular smooth muscle cells (VSMCs), which display remarkable phenotypic plasticity during the development of vascular diseases, such as atherosclerosis. Recent studies have shown that VSMCs contribute to the development of atherosclerotic plaques by clonal expansion and transdifferentiation to macrophage-like cells. VSMCs express a variety of cGMP generators and effectors, including NO-sensitive guanylyl cyclase (NO-GC) and cGMP-dependent protein kinase type I (cGKI), respectively. According to the traditional view, cGMP inhibits VSMC proliferation, but this concept has been challenged by recent findings supporting a stimulatory effect of the NO-cGMP-cGKI axis on VSMC growth. Here, we summarize the relevant studies with a focus on VSMC growth regulation by the NO-cGMP-cGKI pathway in cultured VSMCs and mouse models of atherosclerosis, restenosis, and angiogenesis. We discuss potential reasons for inconsistent results, such as the use of genetic versus pharmacological approaches and primary versus subcultured cells. We also explore how modern methods for cGMP imaging and cell tracking could help to improve our understanding of cGMP’s role in vascular plasticity. We present a revised model proposing that cGMP promotes phenotypic switching of contractile VSMCs to VSMC-derived plaque cells in atherosclerotic lesions. Regulation of vascular remodeling by cGMP is not only an interesting new therapeutic strategy, but could also result in side effects of clinically used cGMP-elevating drugs.http://www.mdpi.com/2308-3425/5/2/20cyclic guanosine 3′-5′ monophosphatenitric oxidevascular smooth muscle cellscGMP-dependent protein kinase type Iatherosclerosiscell plasticitytransdifferentiationcell fate mappingimaging |
| spellingShingle | Moritz Lehners Hyazinth Dobrowinski Susanne Feil Robert Feil cGMP Signaling and Vascular Smooth Muscle Cell Plasticity Journal of Cardiovascular Development and Disease cyclic guanosine 3′-5′ monophosphate nitric oxide vascular smooth muscle cells cGMP-dependent protein kinase type I atherosclerosis cell plasticity transdifferentiation cell fate mapping imaging |
| title | cGMP Signaling and Vascular Smooth Muscle Cell Plasticity |
| title_full | cGMP Signaling and Vascular Smooth Muscle Cell Plasticity |
| title_fullStr | cGMP Signaling and Vascular Smooth Muscle Cell Plasticity |
| title_full_unstemmed | cGMP Signaling and Vascular Smooth Muscle Cell Plasticity |
| title_short | cGMP Signaling and Vascular Smooth Muscle Cell Plasticity |
| title_sort | cgmp signaling and vascular smooth muscle cell plasticity |
| topic | cyclic guanosine 3′-5′ monophosphate nitric oxide vascular smooth muscle cells cGMP-dependent protein kinase type I atherosclerosis cell plasticity transdifferentiation cell fate mapping imaging |
| url | http://www.mdpi.com/2308-3425/5/2/20 |
| work_keys_str_mv | AT moritzlehners cgmpsignalingandvascularsmoothmusclecellplasticity AT hyazinthdobrowinski cgmpsignalingandvascularsmoothmusclecellplasticity AT susannefeil cgmpsignalingandvascularsmoothmusclecellplasticity AT robertfeil cgmpsignalingandvascularsmoothmusclecellplasticity |