Exploring the difference in the mechanics of vascular smooth muscle cells from wild-type and apolipoprotein-E knockout mice.
Alex P RickelHanna J SanyourCourtney KinserNisha KhatiwadaHayley VogelZhongkui HongPublished in: American journal of physiology. Cell physiology (2022)
Atherosclerosis-related cardiovascular diseases are a leading cause of mortality worldwide. Vascular smooth muscle cells (VSMCs) comprise the medial layer of the arterial wall and undergo phenotypic switching during atherosclerosis to a synthetic phenotype capable of proliferation and migration. The surrounding environment undergoes alterations in extracellular matrix (ECM) stiffness and composition and an increase in cholesterol content. Using an atherosclerotic murine model, we analyzed how the mechanics of VSMCs isolated from Western diet-fed apolipoprotein-E knockout ( ApoE -/- ) and wild-type (WT) mice were altered during atherosclerosis. Increased stiffness of ApoE -/- VSMCs correlated with a greater degree of stress fiber alignment, as evidenced by atomic force microscopy (AFM)-generated force maps and stress fiber topography images. On type-1 collagen (COL1)-coated polyacrylamide (PA) gels (referred to as substrate) of varying stiffness, ApoE -/- VSMCs had lower adhesion forces to COL1 and N-cadherin (N-Cad) compared with WT cells. ApoE -/- VSMC stiffness was significantly greater than that of WT cells. Cell stiffness increased with increasing substrate stiffness for both ApoE -/- and WT VSMCs. In addition, ApoE -/- VSMCs showed an enhanced migration capability on COL1-coated substrates and a general decreasing trend in migration capacity with increasing substrate stiffness, correlating with lowered adhesion forces as compared with WT VSMCs. Altogether, these results demonstrate the potential contribution of the alteration in VSMC mechanics in the development of atherosclerosis.
Keyphrases
- vascular smooth muscle cells
- wild type
- angiotensin ii
- cognitive decline
- cardiovascular disease
- high fat diet
- extracellular matrix
- atomic force microscopy
- induced apoptosis
- high speed
- coronary artery disease
- physical activity
- deep learning
- metabolic syndrome
- endoplasmic reticulum stress
- single molecule
- mesenchymal stem cells
- adipose tissue
- risk factors
- staphylococcus aureus
- cell proliferation
- biofilm formation
- amino acid
- south africa
- cell therapy
- cell migration
- mass spectrometry
- cell adhesion
- drug induced
- low density lipoprotein