scholarly journals Vascular Smooth Muscle Cell-Specific Progerin Expression Provokes Contractile Impairment in a Mouse Model of Hutchinson-Gilford Progeria Syndrome that Is Ameliorated by Nitrite Treatment

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 656 ◽  
Author(s):  
Lara del Campo ◽  
Amanda Sánchez-López ◽  
Cristina González-Gómez ◽  
María Jesús Andrés-Manzano ◽  
Beatriz Dorado ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Endothelial Dysfunction ◽  
Mouse Model ◽  
Vascular Smooth Muscle ◽  
Vascular Tone ◽  
Genetic Disorder ◽  
Cell Types ◽  
Dietary Sodium ◽  
Progeria Syndrome ◽  
Hutchinson Gilford Progeria Syndrome

Cardiovascular disease (CVD) is the main cause of death worldwide, and aging is its leading risk factor. Aging is much accelerated in Hutchinson–Gilford progeria syndrome (HGPS), an ultra-rare genetic disorder provoked by the ubiquitous expression of a mutant protein called progerin. HGPS patients die in their teens, primarily due to cardiovascular complications. The primary causes of age-associated CVD are endothelial dysfunction and dysregulated vascular tone; however, their contribution to progerin-induced CVD remains poorly characterized. In the present study, we found that progeroid LmnaG609G/G609G mice with ubiquitous progerin expression show both endothelial dysfunction and severe contractile impairment. To assess the relative contribution of specific vascular cell types to these anomalies, we examined LmnaLCS/LCSTie2Cretg/+ and LmnaLCS/LCSSm22αCretg/+ mice, which express progerin specifically in endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), respectively. Whereas vessel contraction was impaired in mice with VSMC-specific progerin expression, we observed no endothelial dysfunction in mice with progerin expression restricted to VSMCs or ECs. Vascular tone regulation in progeroid mice was ameliorated by dietary sodium nitrite supplementation. Our results identify VSMCs as the main cell type causing contractile impairment in a mouse model of HGPS that is ameliorated by nitrite treatment.

scholarly journals Vascular smooth muscle cell‐specific progerin expression in a mouse model of Hutchinson–Gilford progeria syndrome promotes arterial stiffness: Therapeutic effect of dietary nitrite

Aging Cell ◽  
2019 ◽  
Vol 18 (3) ◽  
pp. e12936 ◽  
Author(s):  
Lara del Campo ◽  
Amanda Sánchez‐López ◽  
Mercedes Salaices ◽  
Ryan A. von Kleeck ◽  
Elba Expósito ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Arterial Stiffness ◽  
Mouse Model ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Therapeutic Effect ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Progeria Syndrome ◽  
Hutchinson Gilford Progeria Syndrome

scholarly journals Vascular Smooth Muscle–Specific Progerin Expression Accelerates Atherosclerosis and Death in a Mouse Model of Hutchinson-Gilford Progeria Syndrome

Circulation ◽  
2018 ◽  
Vol 138 (3) ◽  
pp. 266-282 ◽  
Author(s):  
Magda R. Hamczyk ◽  
Ricardo Villa-Bellosta ◽  
Pilar Gonzalo ◽  
María J. Andrés-Manzano ◽  
Paula Nogales ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Mouse Model ◽  
Vascular Smooth Muscle ◽  
Progeria Syndrome ◽  
Hutchinson Gilford Progeria Syndrome

scholarly journals Progressive vascular smooth muscle cell defects in a mouse model of Hutchinson-Gilford progeria syndrome

2006 ◽  
Vol 103 (9) ◽  
pp. 3250-3255 ◽  
Author(s):  
R. Varga ◽  
M. Eriksson ◽  
M. R. Erdos ◽  
M. Olive ◽  
I. Harten ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Mouse Model ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Progeria Syndrome ◽  
Hutchinson Gilford Progeria Syndrome

Progressive vascular smooth muscle defects in a mouse model of Hutchinson–Gilford Progeria Syndrome

2006 ◽  
Vol 45 (3) ◽  
pp. e65
Author(s):  
Renu Vermani ◽  
Michelle Olive ◽  
Tom Wright ◽  
Francis Collins ◽  
Elizabeth Nabel ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Mouse Model ◽  
Vascular Smooth Muscle ◽  
Progeria Syndrome ◽  
Hutchinson Gilford Progeria Syndrome

scholarly journals Premature Vascular Aging with Features of Plaque Vulnerability in an Atheroprone Mouse Model of Hutchinson–Gilford Progeria Syndrome with Ldlr Deficiency

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2252
Author(s):  
Rosa M. Nevado ◽  
Magda R. Hamczyk ◽  
Pilar Gonzalo ◽  
María Jesús Andrés-Manzano ◽  
Vicente Andrés
Keyword(s):  
Smooth Muscle ◽  
Mouse Model ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Genetic Diseases ◽  
Nuclear Lamina ◽  
Reduced Body ◽  
Unstable Plaques ◽  
Progeria Syndrome ◽  
Hutchinson Gilford Progeria Syndrome

Hutchinson–Gilford progeria syndrome (HGPS) is among the most devastating of the laminopathies, rare genetic diseases caused by mutations in genes encoding nuclear lamina proteins. HGPS patients age prematurely and die in adolescence, typically of atherosclerosis-associated complications. The mechanisms of HGPS-related atherosclerosis are not fully understood due to the scarcity of patient-derived samples and the availability of only one atheroprone mouse model of the disease. Here, we generated a new atherosusceptible model of HGPS by crossing progeroid LmnaG609G/G609G mice, which carry a disease-causing mutation in the Lmna gene, with Ldlr−/− mice, a commonly used preclinical atherosclerosis model. Ldlr−/−LmnaG609G/G609G mice aged prematurely and had reduced body weight and survival. Compared with control mice, Ldlr−/−LmnaG609G/G609G mouse aortas showed a higher atherosclerosis burden and structural abnormalities typical of HGPS patients, including vascular smooth muscle cell depletion in the media, adventitial thickening, and elastin structure alterations. Atheromas of Ldlr−/−LmnaG609G/G609G mice had features of unstable plaques, including the presence of erythrocytes and iron deposits and reduced smooth muscle cell and collagen content. Ldlr−/−LmnaG609G/G609G mice faithfully recapitulate vascular features found in patients and thus provide a new tool for studying the mechanisms of HGPS-related atherosclerosis and for testing therapies.

scholarly journals The Four-and-a-half LIM Domain Protein 2 Regulates Vascular Smooth Muscle Phenotype and Vascular Tone

2009 ◽  
Vol 284 (19) ◽  
pp. 13202-13212 ◽  
Author(s):  
Nicole A. Neuman ◽  
Susan Ma ◽  
Gavin R. Schnitzler ◽  
Yan Zhu ◽  
Giorgio Lagna ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Vascular Tone ◽  
Lim Domain ◽  
Lim Domain Protein ◽  
Domain Protein

scholarly journals Pressure-induced constriction is inhibited in a mouse model of reduced βENaC

2009 ◽  
Vol 297 (3) ◽  
pp. R723-R728 ◽  
Author(s):  
Lauren G. VanLandingham ◽  
Kimberly P. Gannon ◽  
Heather A. Drummond
Keyword(s):  
Smooth Muscle ◽  
Mouse Model ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Cerebral Arteries ◽  
Muscle Cells ◽  
Normal Pressure ◽  
Quantitative Immunofluorescence ◽  
Mechanosensitive Ion Channel

Recent studies suggest certain epithelial Na+channel (ENaC) proteins may be components of mechanosensitive ion channel complexes in vascular smooth muscle cells that contribute to pressure-induced constriction in middle cerebral arteries (MCA). However, the role of a specific ENaC protein, βENaC, in pressure-induced constriction of MCAs has not been determined. The goal of this study was to determine whether pressure-induced constriction in the MCA is altered in a mouse model with reduced levels of βENaC. Using quantitative immunofluorescence, we found whole cell βENaC labeling in cerebral vascular smooth muscle cells (VSMCs) was suppressed 46% in βENaC homozygous mutant (m/m) mice compared with wild-type littermates (+/+). MCAs from βENaC +/+ and m/m mice were isolated and placed in a vessel chamber for myographic analysis. Arteries from βENaC+/+ mice constricted to stepwise increases in perfusion pressure and developed maximal tone of 10 ± 2% at 90 mmHg ( n = 5). In contrast, MCAs from βENaC m/m mice developed significantly less tone (4 ± 1% at 90 mmHg, n = 5). Vasoconstrictor responses to KCl (4–80 mM) were identical between genotypes and responses to phenylephrine (10−7-10−4M) were marginally altered, suggesting that reduced levels of VSMC βENaC specifically inhibit pressure-induced constriction. Our findings indicate βENaC is required for normal pressure-induced constriction in the MCA and provide further support for the hypothesis that βENaC proteins are components of a mechanosensor in VSMCs.

The role of globins in cardiovascular physiology

2021 ◽  
Author(s):  
T.C. Steven Keller ◽  
Christophe Lechauve ◽  
Alexander S Keller ◽  
Steven Brooks ◽  
Mitchell J Weiss ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Central Nervous System ◽  
Nervous System ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Cell Types ◽  
Specific Cell ◽  
In Cells

Globin proteins exist in every cell type of the vasculature, from erythrocytes to endothelial cells, vascular smooth muscle cells, and peripheral nerve cells. Many globin subtypes are also expressed in muscle tissues (including cardiac and skeletal muscle), in other organ-specific cell types, and in cells of the central nervous system. The ability of each of these globins to interact with molecular oxygen (O2) and nitric oxide (NO) is preserved across these contexts. Endothelial α-globin is an example of extra-erythrocytic globin expression. Other globins, including myoglobin, cytoglobin, and neuroglobin are observed in other vascular tissues. Myoglobin is observed primarily in skeletal muscle and smooth muscle cells surrounding the aorta or other large arteries. Cytoglobin is found in vascular smooth muscle but can also be expressed in non-vascular cell types, especially in oxidative stress conditions after ischemic insult. Neuroglobin was first observed in neuronal cells, and its expression appears to be restricted mainly to the central and peripheral nervous systems. Brain and central nervous system neurons expressing neuroglobin are positioned close to many arteries within the brain parenchyma and can control smooth muscle contraction and, thus, tissue perfusion and vascular reactivity. Overall, reactions between NO and globin heme-iron contribute to vascular homeostasis by regulating vasodilatory NO signals and scaveging reactive species in cells of the mammalian vascular system. Here, we discuss how globin proteins affect vascular physiology with a focus on NO biology, and offer perspectives for future study of these functions.

Sign in / Sign up

Export Citation Format

Share Document