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Biomechanical Asses...
Biomechanical Assessment of Macro-Calcification in Human Carotid Atherosclerosis and Its Impact on Smooth Muscle Cell Phenotype
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- Seime, Till (författare)
- Karolinska Inst, Dept Mol Med & Surg, Vasc Surg, S-17164 Stockholm, Sweden.
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- van Wanrooij, Max (författare)
- KTH,KTH Royal Inst Technol, Sch Engn Sci, Solid Mech, S-10044 Stockholm, Sweden.
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- Karlof, Eva (författare)
- Karolinska Institutet
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- Kronqvist, Malin (författare)
- Karolinska Institutet
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- Johansson, Staffan (författare)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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- Matic, Ljubica (författare)
- Karolinska Institutet
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- Gasser, T. Christian (författare)
- KTH,Hållfasthetslära,KTH Royal Inst Technol, Sch Engn Sci, Solid Mech, S-10044 Stockholm, Sweden.
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- Hedin, Ulf (författare)
- Karolinska Institutet
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KTH Karolinska Inst, Dept Mol Med & Surg, Vasc Surg, S-17164 Stockholm, Sweden (creator_code:org_t)
- 2022-10-18
- 2022
- Engelska.
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Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 11:20, s. 3279-
- Relaterad länk:
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.3...
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Abstract
Ämnesord
Stäng
- Intimal calcification and vascular stiffening are predominant features of end-stage atherosclerosis. However, their role in atherosclerotic plaque instability and how the extent and spatial distribution of calcification influence plaque biology remain unclear. We recently showed that extensive macro calcification can be a stabilizing feature of late-stage human lesions, associated with a reacquisition of more differentiated properties of plaque smooth muscle cells (SMCs) and extracellular matrix (ECM) remodeling. Here, we hypothesized that biomechanical forces related to macro-calcification within plaques influence SMC phenotype and contribute to plaque stabilization. We generated a finite element modeling (FEM) pipeline to assess plaque tissue stretch based on image analysis of preoperative computed tomography angiography (CTA) of carotid atherosclerotic plaques to visualize calcification and soft tissues (lipids and extracellular matrix) within the lesions. Biomechanical stretch was significantly reduced in tissues in close proximity to macro calcification, while increased levels were observed within distant soft tissues. Applying this data to an in vitro stretch model on primary vascular SMCs revealed upregulation of typical markers for differentiated SMCs and contractility under low stretch conditions but also impeded SMC alignment. In contrast, high stretch conditions in combination with calcifying conditions induced SMC apoptosis. Our findings suggest that the load bearing capacities of macro calcifications influence SMC differentiation and survival and contribute to atherosclerotic plaque stabilization.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
Nyckelord
- atherosclerosis
- carotid stenosis
- calcification
- biomechanics
- smooth muscle cells
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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