Decreased vascular smooth muscle contractility in Hutchinson–Gilford Progeria Syndrome linked to defective smooth muscle myosin heavy chain expression
| Autor: | Emilia Roberts, Richard K. Assoian, Paola Castagnino, Shefali Talwar, Giovanni Ferrari, Ryan A. von Kleeck |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Adult medicine.medical_specialty Aging congenital hereditary and neonatal diseases and abnormalities Vascular smooth muscle Science Myosin Biochemistry Muscle Smooth Vascular Article Contractility 03 medical and health sciences 0302 clinical medicine Progeria Internal medicine medicine Animals Humans Aorta Aged Aged 80 and over Multidisciplinary Myosin Heavy Chains integumentary system Chemistry nutritional and metabolic diseases Smooth Muscle Myosins Middle Aged Progerin medicine.disease Cardiovascular biology Mice Inbred C57BL 030104 developmental biology Endocrinology Gene Expression Regulation Arterial stiffness Medicine Ectopic expression 030217 neurology & neurosurgery Lamin Muscle Contraction |
| Zdroj: | Scientific Reports, Vol 11, Iss 1, Pp 1-11 (2021) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Children 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. |
| Databáze: | OpenAIRE |
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