scholarly journals Decreased vascular smooth muscle contractility in Hutchinson–Gilford Progeria Syndrome linked to defective smooth muscle myosin heavy chain expression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ryan von Kleeck ◽  
Paola Castagnino ◽  
Emilia Roberts ◽  
Shefali Talwar ◽  
Giovanni Ferrari ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Smooth Muscle Myosin ◽  
Mutant Form ◽  
Wild Type ◽  
Arterial Contractility ◽  
Progeria Syndrome ◽  
Hutchinson Gilford Progeria Syndrome ◽  
Muscle Myosin

AbstractChildren with Hutchinson–Gilford Progeria Syndrome (HGPS) suffer from multiple cardiovascular pathologies due to the expression of progerin, a mutant form of the nuclear envelope protein Lamin A. Progerin expression has a dramatic effect on arterial smooth muscle cells (SMCs) and results in decreased viability and increased arterial stiffness. However, very little is known about how progerin affects SMC contractility. Here, we studied the LaminAG609G/G609G mouse model of HGPS and found reduced arterial contractility at an early age that correlates with a decrease in smooth muscle myosin heavy chain (SM-MHC) mRNA and protein expression. Traction force microscopy on isolated SMCs from these mice revealed reduced force generation compared to wild-type controls; this effect was phenocopied by depletion of SM-MHC in WT SMCs and overcome by ectopic expression of SM-MHC in HGPS SMCs. Arterial SM-MHC levels are also reduced with age in wild-type mice and humans, suggesting a common defect in arterial contractility in HGPS and normal aging.

Expression of Desmin and Smooth Muscle Myosin Heavy Chain in Dermatofibromas

2002 ◽  
Vol 126 (10) ◽  
pp. 1179-1183 ◽  
Author(s):  
Andrea K. Bruecks ◽  
Martin J. Trotter
Keyword(s):  
Smooth Muscle ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Smooth Muscle Actin ◽  
Smooth Muscle Myosin ◽  
Immunoperoxidase Staining ◽  
Muscle Actin ◽  
Muscle Myosin ◽  
Hematoxylin Eosin ◽  
Focal Expression

Abstract Background.—The histopathologic features of dermatofibroma vary remarkably, and this diversity may occasionally cause problems in differentiating between benign and malignant mesenchymal lesions, including smooth muscle neoplasms. Immunohistochemical stains are sometimes necessary to clarify the histogenesis of a lesion. Objective.—To evaluate dermatofibromas for expression of desmin and smooth muscle myosin heavy chain (SM-MHC) antigens, which are commonly used as evidence of smooth muscle differentiation. Methods.—We studied 100 consecutive cases of dermatofibroma using hematoxylin-eosin–stained sections and immunoperoxidase staining with antibodies against desmin, SM-MHC, and smooth muscle actin. Results.—We found focal positivity for desmin in 9 cases, and in 2 of these cases, at least 10% of lesional cells showed strong expression. We found focal staining for SM-MHC in 10 cases, and in 2 of these cases, at least 10% of the lesional cells were positive. Regions positive for desmin and/or SM-MHC did not show definite histologic features of myogenous differentiation on hematoxylin-eosin–stained sections. All dermatofibromas expressing desmin and SM-MHC were also strongly positive for smooth muscle actin. Conclusions.—About 10% of dermatofibromas show focal expression of desmin and SM-MHC, and this expression may be present in up to 10% to 15% of lesional cells. Thus, in dermal spindle cell lesions, focal expression of these muscle antigens, like that of smooth muscle actin, is not diagnostic of a smooth muscle tumor.

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