Reduced stiffness and augmented traction force in type 2 diabetic coronary microvascular smooth muscle

McCallinhart, Patricia E.; Cho, Youjin; Sun, Zhe; Ghadiali, Samir N.; Meininger, Gerald A.; Trask, Aaron J.

doi:10.1152/ajpheart.00542.2019

Cited by 16 publications

(12 citation statements)

References 46 publications

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“…This should allow for maintenance of the intracellular (cytoskeletal) and extracellular matrix structures that affect the mechanical properties of the vascular wall. Indeed, it has been shown that cytoskeletal structures, such as Factin stress fibers, as well as extracellular matrix components, such as elastin and collagen, participate in providing mechanical strength to the vascular wall under passive conditions, albeit each at different intravascular pressures (113)(114)(115)(116)(117)(118)(119)(120). In addition, to avoid a major involvement of the axial component in the strain and stress assessment, vessels should be extended to eliminate any bending or bowing at the maximal intraluminal pressure used.…”

Section: Mechanical Analysismentioning

confidence: 99%

Guidelines for the measurement of vascular function and structure in isolated arteries and veins

Wenceslau

Earley

England

et al. 2021

American Journal of Physiology-Heart and Circulatory Physiology

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The measurement of vascular function in isolated vessels has revealed important insights into the structural, functional, and biomechanical features of the normal and diseased cardiovascular system, and has provided a molecular understanding of the cells that constitutes arteries and veins and their interaction. Further, this approach has allowed the discovery of vital pharmacological treatments for cardiovascular diseases. However, the expansion of the vascular physiology field has also brought new concerns over scientific rigor and reproducibility. Therefore, it is appropriate to set guidelines for the best practices of evaluating vascular function in isolated vessels. These guidelines are a comprehensive document detailing the best practices and pitfalls for the assessment of function in large and small arteries and veins. Herein, we bring together experts in the field of vascular physiology with the purpose of developing guidelines for evaluating ex vivo vascular function. By utilizing this document, vascular physiologists will have consistency amongst methodological approaches, producing more reliable and reproducible results.

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Section: Mechanical Analysismentioning

confidence: 99%

Guidelines for the measurement of vascular function and structure in isolated arteries and veins

Wenceslau

Earley

England

et al. 2021

American Journal of Physiology-Heart and Circulatory Physiology

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“…Regional micromechanics of grafts were measured using atomic force microscopy (AFM). 28 – 30 Tissue sections were de-paraffinized with xylene washes and rehydrated through graded alcohols, followed by overnight immersion in PBS at room temperature. Micromechanical properties of tissue samples were characterized using the Asylum MFP-3D-Infinity-BIO AFM.…”

Section: Methodsmentioning

confidence: 99%

“…The Young’s modulus of each point was determined by fitting force-indentation data from 40 curves to the Oliver-Pharr model (a modified Hertz model) using IGOR Pro software (WaveMetrics). 28 , 33 …”

Section: Methodsmentioning

confidence: 99%

Regeneration of partially decellularized tracheal scaffolds in a mouse model of orthotopic tracheal replacement

et al. 2021

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Decellularized tracheal scaffolds offer a potential solution for the repair of long-segment tracheal defects. However, complete decellularization of trachea is complicated by tracheal collapse. We created a partially decellularized tracheal scaffold (DTS) and characterized regeneration in a mouse model of tracheal transplantation. All cell populations except chondrocytes were eliminated from DTS. DTS maintained graft integrity as well as its predominant extracellular matrix (ECM) proteins. We then assessed the performance of DTS in vivo. Grafts formed a functional epithelium by study endpoint (28 days). While initial chondrocyte viability was low, this was found to improve in vivo. We then used atomic force microscopy to quantify micromechanical properties of DTS, demonstrating that orthotopic implantation and graft regeneration lead to the restoration of native tracheal rigidity. We conclude that DTS preserves the cartilage ECM, supports neo-epithelialization, endothelialization and chondrocyte viability, and can serve as a potential solution for long-segment tracheal defects.

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“…Atomic force microscopy (AFM) provides nanoscale resolution of the biomechanical properties of soft biological tissues, including the vasculature [ 17 , 19 ]. AFM-based studies have successfully uncovered changes in arterial stiffness in response to hypertension [ 14 , 20 ], diabetes [ 21 , 22 ], and aging [ 14 , 23 ], but to our knowledge, it has not been used to map sex-related differences in media-layer stiffness under physiological conditions. Another useful technique to interrogate arterial stiffness is via functional studies incorporating uniaxial circumferential loading in a wire myograph.…”

Section: Introductionmentioning

confidence: 99%

“…Another useful technique to interrogate arterial stiffness is via functional studies incorporating uniaxial circumferential loading in a wire myograph. Large artery compliance is tightly regulated by VSM reactive properties, including contraction and relaxation [ 24 ], and there seems to be a linear relationship between stiffness and traction force development [ 25 ], which has been confirmed in diabetic coronary microvascular SMCs [ 21 ]. However, how AFM-based medial-layer stiffness results associate with force development in isolated aortas is unknown.…”

Section: Introductionmentioning

confidence: 99%

Connecting Aortic Stiffness to Vascular Contraction: Does Sex Matter?

Oliveira

Priviero

Delgado

et al. 2022

IJMS

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This study was designed to connect aortic stiffness to vascular contraction in young male and female Wistar rats. We hypothesized that female animals display reduced intrinsic media-layer stiffness, which associates with improved vascular function. Atomic force microscopy (AFM)-based nanoindentation analysis was used to derive stiffness (Young’s modulus) in biaxially (i.e., longitudinal and circumferential) unloaded aortic rings. Reactivity studies compatible with uniaxial loading (i.e., circumferential) were used to assess vascular responses to a selective α1 adrenergic receptor agonist in the presence or absence of extracellular calcium. Elastin and collagen levels were indirectly evaluated with fluorescence microscopy and a picrosirius red staining kit, respectively. We report that male and female Wistar rats display similar AFM-derived aortic media-layer stiffness, even though female animals withstand higher aortic intima-media thickness-to-diameter ratio than males. Female animals also present reduced phenylephrine-induced aortic force development in concentration-response and time-force curves. Specifically, we observed impaired force displacement in both parts of the contraction curve (Aphasic and Atonic) in experiments conducted with and without extracellular calcium. Additionally, collagen levels were lower in female animals without significant elastin content and fragmentation changes. In summary, sex-related functional differences in isolated aortas appear to be related to dissimilarities in the dynamics of vascular reactivity and extracellular matrix composition rather than a direct response to a shift in intrinsic media-layer stiffness.

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Reduced stiffness and augmented traction force in type 2 diabetic coronary microvascular smooth muscle

Cited by 16 publications

References 46 publications

Guidelines for the measurement of vascular function and structure in isolated arteries and veins

Guidelines for the measurement of vascular function and structure in isolated arteries and veins

Regeneration of partially decellularized tracheal scaffolds in a mouse model of orthotopic tracheal replacement

Connecting Aortic Stiffness to Vascular Contraction: Does Sex Matter?

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