Role of Vascular Smooth Muscle Cell Phenotype Switching in Arteriogenesis

Arteriogenesis is one of the primary physiological means by which the circulatory collateral system restores blood flow after significant arterial occlusion in peripheral arterial disease patients. Vascular smooth muscle cells (VSMCs) are the predominant cell type in collateral arteries and respond to altered blood flow and inflammatory conditions after an arterial occlusion by switching their phenotype between quiescent contractile and proliferative synthetic states. Maintaining the contractile state of VSMC is required for collateral vascular function to regulate blood vessel tone and blood flow during arteriogenesis, whereas synthetic SMCs are crucial in the growth and remodeling of the collateral media layer to establish more stable conduit arteries. Timely VSMC phenotype switching requires a set of coordinated actions of molecular and cellular mediators to result in an expansive remodeling of collaterals that restores the blood flow effectively into downstream ischemic tissues. This review overviews the role of VSMC phenotypic switching in the physiological arteriogenesis process and how the VSMC phenotype is affected by the primary triggers of arteriogenesis such as blood flow hemodynamic forces and inflammation. Better understanding the role of VSMC phenotype switching during arteriogenesis can identify novel therapeutic strategies to enhance revascularization in peripheral arterial disease.

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MicroRNA‑15b participates in the development of peripheral arterial disease by modulating the growth of vascular smooth muscle cells

Experimental and Therapeutic Medicine ◽

10.3892/etm.2019.7552 ◽

2019 ◽

Cited By ~ 1

Author(s):

Yong Sun ◽

Yong Gao ◽

Tao Song ◽

Chaowen Yu ◽

Zhonglin Nie ◽

...

Keyword(s):

Smooth Muscle ◽

Peripheral Arterial Disease ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cells ◽

Vascular Smooth Muscle Cells ◽

Muscle Cells ◽

Arterial Disease ◽

Peripheral Arterial

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MicroRNA-153-3p Inhibits Cell Proliferation and Increases Apoptosis in Human Vascular Smooth Muscle Cells in Peripheral Arterial Disease

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2020.2303 ◽

2020 ◽

Vol 10 (5) ◽

pp. 632-639

Author(s):

Ran Lu ◽

Xiaohu Yang

Keyword(s):

Smooth Muscle ◽

Peripheral Arterial Disease ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cells ◽

Cell Viability ◽

Vascular Smooth Muscle Cells ◽

Muscle Cells ◽

Arterial Disease ◽

And Migration ◽

Peripheral Arterial

Objective: This study explored the role and molecular mechanism of microRNA-153-3p (miR-1533p) in human vascular smooth muscle cells in peripheral arterial disease. Methods: Human vascular smooth muscle cells (hVSMCs) were transfected with mimic control, miR-153-3p mimic, inhibitor control or miR-153-3p inhibitor for 48 h, and qRT-PCR was applied to determine the transfection efficiency. Meanwhile, the cell viability, cell migration and apoptosis of the transfected cells were measured via MTT assay, flow cytometry analysis and Transwell assay respectively. The target gene of miR-153-3p was predicted by TargetScan and verified by the dual luciferase reporter gene system. In addition, mimic control, miR-153-3p mimic, miR-153-3p mimic + control-plasmid, or miR-153-3p mimic+BCL2-plasmid was transfected into hVSMCs for 48 h, and the cell viability, migration and apoptosis were determined. Besides, qRT-PCR and Western blot assay were applied to measure the expression of BCL2 at both mRNA and protein levels in hVSMCs after the transfection. Results: Compared with the control group, miR-153-3p mimic improved the expression of miR-153-3p, and miR-153-3p inhibitor down-regulated miR-153-3p in hVSMCs. miR-153-3p mimic could reduce the cell viability and migration, and induce the cell apoptosis of hVSMCs. However, miR-153-3p inhibitor had the opposite effects on the cell viability, migration and apoptosis on hVSMCs. We predicted and verified that BCL2 was a direct target of miR-153-3p. In addition, all the effects of miR-153-3p mimic on hVSMCs were significantly reversed by BCL2-plasmid. Conclusion: We demonstrated that miR-153-3p participated in the development and progression of peripheral arterial disease through regulating the proliferation and migration of vascular smooth muscle cells by targeting BCL2.

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Hallucal thenar index: A new index to detect peripheral arterial disease using laser speckle flowgraphy

Vascular ◽

10.1177/1708538120938935 ◽

2020 ◽

pp. 170853812093893

Author(s):

Kazuhiro Tsunekawa ◽

Fumio Nagai ◽

Tamon Kato ◽

Ikkei Takashimizu ◽

Daisuke Yanagisawa ◽

...

Keyword(s):

Blood Flow ◽

Peripheral Arterial Disease ◽

Operating Characteristic ◽

Ankle Brachial Index ◽

Arterial Disease ◽

Laser Speckle ◽

Laser Speckle Flowgraphy ◽

Skin Perfusion ◽

Peripheral Arterial ◽

Cutaneous Blood

Objectives Laser speckle flowgraphy is a technology using reflected scattered light for visualization of blood distribution, which can be used to measure relative velocity of blood flow easily without contact with the skin within a short time. It was hypothesized that laser speckle flowgraphy may be able to identify foot ischemia. This study was performed to determine whether laser speckle flowgraphy could distinguish between subjects with and without peripheral arterial disease. Materials and methods All subjects were classified based on clinical observations using the Rutherford classification: non-peripheral arterial disease, class 0; peripheral arterial disease group, class 2–5. Rutherford class 6 was one of the exclusion criteria. Laser speckle flowgraphy measured the beat strength of skin perfusion as an indicator of average dynamic cutaneous blood flow change synchronized with the heartbeat. The beat strength of skin perfusion indicates the strength of the heartbeat on the skin, and the heartbeat strength calculator in laser speckle flowgraphy uses the blood flow data to perform a Fourier transform to convert the temporal changes in blood flow to a power spectrum. A total of 33 subjects with peripheral arterial disease and 40 subjects without peripheral arterial disease at a single center were prospectively examined. Laser speckle flowgraphy was used to measure hallucal and thenar cutaneous blood flow, and the measurements were repeated three times. The hallucal and thenar index was defined as the ratio of beat strength of skin perfusion value on hallux/beat strength of skin perfusion value on ipsilateral thenar eminence. The Mann–Whitney U-test was used to compare the median values of hallucal and thenar index and ankle brachial index between the two groups. A receiver operating characteristic curve for hallucal and thenar index of beat strength of skin perfusion was plotted, and a cutoff point was set. The correlation between hallucal and thenar index of beat strength of skin perfusion and ankle brachial index was explored in all subjects, the hemodialysis group, and the non-hemodialysis (non-hemodialysis) group. Results The median value of the hallucal and thenar index of beat strength of skin perfusion was significantly different between subjects with and without peripheral arterial disease (0.27 vs. 0.87, respectively; P < 0.001). The median value of ankle brachial index was significantly different between subjects with and without peripheral arterial disease (0.8 vs. 1.1, respectively; P < 0.001). Based on the receiver operating characteristic of hallucal and thenar index, the cutoff was 0.4416 and the sensitivity, specificity, positive predictive value, and negative predictive value were 68.7%, 95%, 91.7%, and 77.6%, respectively. The correlation coefficients of all subjects, the hemodialysis group, and the non-hemodialysis group were 0.486, 0.102, and 0.743, respectively. Conclusions Laser speckle flowgraphy is a noninvasive, rapid, and widely applicable method. Laser speckle flowgraphy using hallucal and thenar index would be helpful to determine the differences between subjects with and without peripheral arterial disease. The correlation between hallucal and thenar index of beat strength of skin perfusion and ankle brachial index indicated that this index was especially useful in the non-hemodialysis group.

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The Role of Circulating Biomarkers in Peripheral Arterial Disease

International Journal of Molecular Sciences ◽

10.3390/ijms22073601 ◽

2021 ◽

Vol 22 (7) ◽

pp. 3601

Author(s):

Goren Saenz-Pipaon ◽

Esther Martinez-Aguilar ◽

Josune Orbe ◽

Arantxa González Miqueo ◽

Leopoldo Fernandez-Alonso ◽

...

Keyword(s):

Peripheral Arterial Disease ◽

Lower Limb ◽

Prediction Models ◽

Arterial Disease ◽

Cardiac Damage ◽

Thrombotic Occlusion ◽

Medical Treatments ◽

Peripheral Arterial ◽

Inflammatory Molecules

Peripheral arterial disease (PAD) of the lower extremities is a chronic illness predominantly of atherosclerotic aetiology, associated to traditional cardiovascular (CV) risk factors. It is one of the most prevalent CV conditions worldwide in subjects >65 years, estimated to increase greatly with the aging of the population, becoming a severe socioeconomic problem in the future. The narrowing and thrombotic occlusion of the lower limb arteries impairs the walking function as the disease progresses, increasing the risk of CV events (myocardial infarction and stroke), amputation and death. Despite its poor prognosis, PAD patients are scarcely identified until the disease is advanced, highlighting the need for reliable biomarkers for PAD patient stratification, that might also contribute to define more personalized medical treatments. In this review, we will discuss the usefulness of inflammatory molecules, matrix metalloproteinases (MMPs), and cardiac damage markers, as well as novel components of the liquid biopsy, extracellular vesicles (EVs), and non-coding RNAs for lower limb PAD identification, stratification, and outcome assessment. We will also explore the potential of machine learning methods to build prediction models to refine PAD assessment. In this line, the usefulness of multimarker approaches to evaluate this complex multifactorial disease will be also discussed.

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Laser Doppler blood flowmeter as a useful instrument for the early detection of lower extremity peripheral arterial disease in hemodialysis patients: an observational study

BMC Nephrology ◽

10.1186/s12882-019-1653-y ◽

2019 ◽

Vol 20 (1) ◽

Author(s):

Takeo Ishii ◽

Shizuka Takabe ◽

Yuki Yanagawa ◽

Yuko Ohshima ◽

Yasuhiro Kagawa ◽

...

Keyword(s):

Blood Flow ◽

Peripheral Arterial Disease ◽

Early Stage ◽

Arterial Disease ◽

Hemodialysis Patients ◽

Laser Doppler ◽

Doppler Flowmetry ◽

Skin Perfusion ◽

Dorsal Area ◽

Peripheral Arterial

Abstract Background A simpler method for detecting atherosclerosis obliterans is required in the clinical setting. Laser Doppler flowmetry (LDF) is easy to perform and can accurately detect deterioration in skin perfusion. We performed LDF for hemodialysis patients to determine the correlations between blood flow in the lower limbs and peripheral arterial disease (PAD). Methods This retrospective study included 128 hemodialysis patients. Patients were categorized into the non-PAD group (n = 106) and PAD group (n = 22), 14 early stage PAD patients were included in the PAD group. We conducted LDF for the plantar area and dorsal area of the foot and examined skin perfusion pressure (SPP) during dialysis. Results SPP-Dorsal Area values were 82.1 ± 22.0 mmHg in the non-PAD, and 59.1 ± 20.3 mmHg in PAD group, respectively (p < 0.05). The LDF-Plantar blood flow (Qb) values were 32.7 ± 15.5 mL/min in non-PAD group and 21.5 ± 11.3 mL/min in PAD group (p < 0.001). A total of 21 non-PAD patients underwent LDF before and during dialysis. The LDF-Plantar-Qb values were 36.5 ± 17.6 mL/min before dialysis and 29.6 ± 17.7 mL/min after dialysis (p < 0.05). We adjusted SPP and LDF for PAD using logistic regression, SPP-Dorsal-Area and LDF-P were significantly correlated with PAD (p < 0.05). The receiver-operating characteristic curve analysis indicated cut-off values of 20.0 mL/min for LDF-Plantar-Qb during dialysis. Conclusion LDF is a simple technique for sensitive detection of early-stage PAD. This assessment will help physicians identify early-stage PAD, including Fontaine stage II in clinical practice, thereby allowing prompt treatment.

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The role of mitochondrial bioenergetics and reactive oxygen species in coronary collateral growth

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00077.2013 ◽

2013 ◽

Vol 305 (9) ◽

pp. H1275-H1280 ◽

Cited By ~ 7

Author(s):

Yuh Fen Pung ◽

Wai Johnn Sam ◽

James P. Hardwick ◽

Liya Yin ◽

Vahagn Ohanyan ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Protein Synthesis ◽

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Energy Production ◽

Phenotypic Switching ◽

Oxygen Species ◽

Coronary Collateral ◽

Collateral Growth

Coronary collateral growth is a process involving coordination between growth factors expressed in response to ischemia and mechanical forces. Underlying this response is proliferation of vascular smooth muscle and endothelial cells, resulting in an enlargement in the caliber of arterial-arterial anastomoses, i.e., a collateral vessel, sometimes as much as an order of magnitude. An integral element of this cell proliferation is the process known as phenotypic switching in which cells of a particular phenotype, e.g., contractile vascular smooth muscle, must change their phenotype to proliferate. Phenotypic switching requires that protein synthesis occurs and different kinase signaling pathways become activated, necessitating energy to make the switch. Moreover, kinases, using ATP to phosphorylate their targets, have an energy requirement themselves. Mitochondria play a key role in the energy production that enables phenotypic switching, but under conditions where mitochondrial energy production is constrained, e.g., mitochondrial oxidative stress, this switch is impaired. In addition, we discuss the potential importance of uncoupling proteins as modulators of mitochondrial reactive oxygen species production and bioenergetics, as well as the role of AMP kinase as an energy sensor upstream of mammalian target of rapamycin, the master regulator of protein synthesis.

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