Medial Arterial Calcification

Ho, Cheng‐Maw; Shanahan, Catherine M.

doi:10.1161/atvbaha.116.306717

Cited by 166 publications

(79 citation statements)

References 78 publications

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“…The mechanisms driving this localized calcification response are poorly understood and likely include novel factors in addition to hyperglycaemia, such as neuropathy. 7 …”

Section: Introductionmentioning

confidence: 99%

Role of smooth muscle cells in vascular calcification: implications in atherosclerosis and arterial stiffness

Durham

Speer

Scatena

et al. 2018

Cardiovascular Research

768

662

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Vascular calcification is associated with a significant increase in all-cause mortality and atherosclerotic plaque rupture. Calcification has been determined to be an active process driven in part by vascular smooth muscle cell (VSMC) transdifferentiation within the vascular wall. Historically, VSMC phenotype switching has been viewed as binary, with the cells able to adopt a physiological contractile phenotype or an alternate ‘synthetic’ phenotype in response to injury. More recent work, including lineage tracing has however revealed that VSMCs are able to adopt a number of phenotypes, including calcific (osteogenic, chondrocytic, and osteoclastic), adipogenic, and macrophagic phenotypes. Whilst the mechanisms that drive VSMC differentiation are still being elucidated it is becoming clear that medial calcification may differ in several ways from the intimal calcification seen in atherosclerotic lesions, including risk factors and specific drivers for VSMC phenotype changes and calcification. This article aims to compare and contrast the role of VSMCs in driving calcification in both atherosclerosis and in the vessel media focusing on the major drivers of calcification, including aging, uraemia, mechanical stress, oxidative stress, and inflammation. The review also discusses novel findings that have also brought attention to specific pro- and anti-calcifying proteins, extracellular vesicles, mitochondrial dysfunction, and a uraemic milieu as major determinants of vascular calcification.

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“…The mechanisms driving this localized calcification response are poorly understood and likely include novel factors in addition to hyperglycaemia, such as neuropathy. 7 …”

Section: Introductionmentioning

confidence: 99%

Role of smooth muscle cells in vascular calcification: implications in atherosclerosis and arterial stiffness

Durham

Speer

Scatena

et al. 2018

Cardiovascular Research

768

662

View full text Add to dashboard Cite

show abstract

“…Vascular calcification is associated with increased cardiovascular morbidity and mortality in patients with atherosclerosis, diabetes and chronic kidney disease (CKD) [ 1 – 3 ]. It is a complex process involving aberrant mineral metabolism, dysregulation of naturally occurring inhibitors of calcification (e.g.…”

Section: Introductionmentioning

confidence: 99%

FTI-277 inhibits smooth muscle cell calcification by up-regulating PI3K/Akt signaling and inhibiting apoptosis

et al. 2018

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BackgroundVascular calcification is associated with increased cardiovascular morbidity and mortality in patients with atherosclerosis, diabetes and chronic kidney disease. However, no viable treatments for this condition have been identified. This study aimed to determine whether farnesyl transferase inhibitors (FTIs) can reduce vascular calcification and the mechanism by which this reduction occurs.ResultsWe demonstrate that FTI-277 significantly inhibits phosphate-induced mineral deposition by vascular smooth muscle cells (VSMC) in vitro, prevents VSMC osteogenic differentiation, and increases mRNA expression of matrix Gla protein (MGP), an inhibitor of mineralization. FTI-277 increases Akt signaling in VSMC in short-term serum-stimulation assays and in long-term mineralization assays. In contrast, manumycin A has no effect on Akt signaling or mineralization. Co-incubation of VSMC with FTI-277 and SH6 (an Akt inhibitor) significantly reduces the inhibitory effect of FTI-277 on mineralization, demonstrating that FTI-277 inhibits calcification by activating Akt signaling. Over-expression of the constitutively active p110 sub-unit of PI3K in VSMC using adenovirus activates Akt, inhibits mineralization, suppresses VSMC differentiation and significantly enhances MGP mRNA expression. FTI-277 also inhibits phosphate-induced activation of caspase 3 and apoptosis of VSMC, and these effects are negated by co-incubation with SH6. Finally, using an ex vivo model of vascular calcification, we demonstrate that FTI-277 inhibits high phosphate-induced mineralization in aortic rings derived from rats with end-stage renal failure.ConclusionsTogether, these results demonstrate that FTI-277 inhibits VSMC mineral deposition by up-regulating PI3K/Akt signaling and preventing apoptosis, suggesting that targeting farnesylation, or Akt specifically, may have therapeutic potential for the prevention of vascular calcification.

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“…Unlike coronary plaques, PAD lesions are usually more fibrous and may contain significant amounts of calcium that often spreads within the tunica media. 57,58 Calcification in the lower extremity, particularly in the setting of diabetes mellitus or chronic kidney disease, 50,51,57,108 doubles cardiovascular mortality and quadruples the risk of amputation, 50,69 but the etiology of FPA calcification remains unclear and is an area of active research. 27,28,50,54,101,103 …”

Section: Femoropopliteal Artery Obstructive Diseasementioning

confidence: 99%

Nitinol Stents in the Femoropopliteal Artery: A Mechanical Perspective on Material, Design, and Performance

et al. 2018

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Endovascular stenting has matured into a commonly used treatment for peripheral arterial disease (PAD) due to its minimally invasive nature and associated reductions in short-termmorbidity and mortality. The mechanical properties of the superelastic Nitinol alloy have played a major role in the explosion of peripheral artery stenting, with modern stents demonstrating reasonable resilience and durability. Yet in the superficial femoral and popliteal arteries, even the newest generation Nitinol stents continue to demonstrate clinical outcomes that leave significant room for improvement. Restenosis and progression of native arterial disease often lead to recurrence of symptoms and reinterventions that increase morbidity and health care expenditures. One of the main factors thought to be associated with stent failure in the femoropopliteal artery (FPA) is the unique and highly dynamic mechanical environment of the lower limb. Clinical and experimental data demonstrate that the FPA undergoes significant deformations with limb flexion. It is hypothesized that the inability of many existing stent designs to conform to these deformations likely plays a role in reconstruction failure, as repetitive movements of the leg and thigh combine with mechanical mismatch between the artery and the stent and result in mechanical damage to both the artery and the stent. In this review we will identify challenges and provide a mechanical perspective of FPA stenting, and then discuss current research directions with promise to provide a better understanding of Nitinol, specific features of stent design, and improved characterization of the biomechanical environment of the FPA to facilitate development of better stents for patients with PAD.

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Medial Arterial Calcification

Cited by 166 publications

References 78 publications

Role of smooth muscle cells in vascular calcification: implications in atherosclerosis and arterial stiffness

Role of smooth muscle cells in vascular calcification: implications in atherosclerosis and arterial stiffness

FTI-277 inhibits smooth muscle cell calcification by up-regulating PI3K/Akt signaling and inhibiting apoptosis

Nitinol Stents in the Femoropopliteal Artery: A Mechanical Perspective on Material, Design, and Performance

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