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Molecular Vascular Physiology

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 August 2021) | Viewed by 36239

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Special Issue Editors

Dr. Maurizio Mandalà

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Guest Editor

Department of Biology, Ecology and Earth Sciences, University of Calabria, 87036 Rende, Italy
Interests: arteries; veins; hypertension; vascular remodeling; pregnancy; preeclampsia
Special Issues, Collections and Topics in MDPI journals

Dr. Daniel Henrion

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Guest Editor

MITOVASC Department, INSERM U1083, CNRS UMR6214, University of Angers, 49055 Angers, France
Interests: blood flow; resistance arteries; endothelium; vascular remodeling; cardiovascular diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The mammalian vascular network needs to be highly plastic in order to meet organ-specific and local demands for nutrients and oxygen. Blood vessels (arteries and veins) play a pivotal role in the regulation of blood flow to the organs by adapting their structure and function. Blood vessels’ reactivity (relaxation/constriction) allows them to change their luminal diameter to regulate organ/tissue perfusion according to its need. The vascular reactivity results mainly from a cross-talk between two types of vascular cells: endothelial cells (ECs) and smooth muscle cells (SMCs). The latter, which are a component of the tunica media (middle layer) of blood vessels, are responsible for the contraction directly involved in settling vessels’ luminal diameter. ECs, which are a component of the inner layer (tunica intima) of blood vessels, act on SMCs to actively control their contraction and, therefore, vessels’ luminal diameter. Both types of cells respond to several physiological factors, including shear stress, intraluminal pressure, hormones, and macromolecules, which activate numerous molecular pathways. Vascular bed differences characterize blood vessels in terms of their function in the organs. Further, the adaptation of blood vessels during development, growth, and aging, but also in response to risk factors such as diabetes, obesity, and hypertension, requires blood vessels to be plastic in response to physiological and pathological stimuli.

This Special Issue on “Molecular Vascular Physiology” focuses on the molecular mechanisms underlying the function of blood vessels under physiological and pathological conditions.

Dr. Maurizio Mandalà
Prof. Dr. Daniel Henrion
Guest Editors

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Keywords

blood vessels
vascular mechanism
endothelial cells
smooth muscle cells
arteries
veins

Published Papers (12 papers)

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15 pages, 2642 KiB

Open AccessArticle

Dual Role of Thrombospondin-1 in Flow-Induced Remodeling

by Céline Grenier, Antoine Caillon, Mathilde Munier, Linda Grimaud, Tristan Champin, Bertrand Toutain, Céline Fassot, Olivier Blanc-Brude and Laurent Loufrani

Int. J. Mol. Sci. 2021, 22(21), 12086; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222112086 - 08 Nov 2021

Viewed by 2269

Abstract

(1) Background: Chronic increases in blood flow, as in cardiovascular diseases, induce outward arterial remodeling. Thrombospondin-1 (TSP-1) is known to interact with matrix proteins and immune cell-surface receptors, but its contribution to flow-mediated remodeling in the microcirculation remains unknown. (2) Methods: Mesenteric arteries were ligated in vivo to generate high- (HF) and normal-flow (NF) arteries in wild-type (WT) and TSP-1-deleted mice (TSP-1^−/−). After 7 days, arteries were isolated and studied ex vivo. (3) Results: Chronic increases in blood flow induced outward remodeling in WT mice (increasing diameter from 221 ± 10 to 280 ± 10 µm with 75 mmHg intraluminal pressure) without significant effect in TSP-1^−/− (296 ± 18 to 303 ± 14 µm), neutropenic or adoptive bone marrow transfer mice. Four days after ligature, pro inflammatory gene expression levels (CD68, Cox2, Gp91phox, p47phox and p22phox) increased in WT HF arteries but not in TSP-1^−/− mice. Perivascular neutrophil accumulation at day 4 was significantly lower in TSP-1^−/− than in WT mice. (4) Conclusions: TSP-1 origin is important; indeed, circulating TSP-1 participates in vasodilation, whereas both circulating and tissue TSP-1 are involved in arterial wall thickness and diameter expansion. Full article

(This article belongs to the Special Issue Molecular Vascular Physiology)

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12 pages, 1668 KiB

Open AccessArticle

Chronic Exposure to HIV-Derived Protein Tat Impairs Endothelial Function via Indirect Alteration in Fat Mass and Nox1-Mediated Mechanisms in Mice

by Laszlo Kovacs, Thiago Bruder-Nascimento, Lindsey Greene, Simone Kennard and Eric J. Belin de Chantemèle

Int. J. Mol. Sci. 2021, 22(20), 10977; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222010977 - 12 Oct 2021

Cited by 6 | Viewed by 1663

Abstract

People living with human immunodeficiency virus (HIV) (PLWH) have increased risk for atherosclerosis-related cardiovascular disease (CVD), the main cause of death in this population. Notwithstanding, the mechanisms of HIV-associated vascular pathogenesis are not fully elucidated. Therefore, we sought to determine whether HIV-regulatory protein Tat mediates HIV-induced endothelial dysfunction via NADPH oxidase 1 (Nox1)-dependent mechanisms. Body weight, fat mass, leptin levels, expression of reactive oxygen species (ROS)-producing enzymes and vascular function were assessed in C57BL/6 male mice treated with Tat for 3 days and 4 weeks. Aortic rings and human endothelial cells were also treated with Tat for 2–24 h in ex vivo and in vitro settings. Chronic (4 weeks) but not acute (3 days and 2–24 h) treatment with Tat decreased body weight, fat mass, and leptin levels and increased the expression of Nox1 and its coactivator NADPH oxidase Activator 1 (NoxA1). This was associated with impaired endothelium-dependent vasorelaxation. Importantly, specific inhibition of Nox1 with GKT771 and chronic leptin infusion restored endothelial function in Tat-treated mice. These data rule out direct effects of HIV-Tat on endothelial function and imply the contribution of reductions in adipose mass and leptin production which likely explain upregulated expression of Nox1 and NoxA1. The Nox1 and leptin system may provide potential targets to improve vascular function in HIV infection-associated CVD. Full article

(This article belongs to the Special Issue Molecular Vascular Physiology)

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11 pages, 2187 KiB

Open AccessArticle

Reduced Endothelial Leptin Signaling Increases Vascular Adrenergic Reactivity in a Mouse Model of Congenital Generalized Lipodystrophy

by Thiago Bruder-Nascimento, Taylor C. Kress, Matthew Pearson, Weiqin Chen, Simone Kennard and Eric J. Belin de Chantemèle

Int. J. Mol. Sci. 2021, 22(19), 10596; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910596 - 30 Sep 2021

Cited by 6 | Viewed by 1795

Abstract

The adipokine leptin, which is best-known for its role in the control of metabolic function, is also a master regulator of cardiovascular function. While leptin has been approved for the treatment of metabolic disorders in patients with congenital generalized lipodystrophy (CGL), the effects of chronic leptin deficiency and the treatment on vascular contractility remain unknown. Herein, we investigated the effects of leptin deficiency and treatment (0.3 mg/day/7 days) on aortic contractility in male Berardinelli-Seip 2 gene deficient mice (gBscl2^-/-, model of CGL) and their wild-type control (gBscl2^+/+), as well as in mice with selective deficiency in endothelial leptin receptor (LepR^EC-/-). Lipodystrophy selectively increased vascular adrenergic contractility via NO-independent mechanisms and induced hypertrophic vascular remodeling. Leptin treatment and Nox1 inhibition blunted adrenergic hypercontractility in gBscl2^-/- mice, however, leptin failed to rescue vascular media thickness. Selective deficiency in endothelial leptin receptor did not alter baseline adrenergic contractility but abolished leptin-mediated reduction in adrenergic contractility, supporting the contribution of endothelium-dependent mechanisms. These data reveal a new direct role for endothelial leptin receptors in the control of vascular contractility and homeostasis, and present leptin as a safe therapy for the treatment of vascular disease in CGL. Full article

(This article belongs to the Special Issue Molecular Vascular Physiology)

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9 pages, 1835 KiB

Open AccessArticle

Endothelium-Derived Hyperpolarizing Factor (EDHF) Mediates Acetylsalicylic Acid (Aspirin) Vasodilation of Pregnant Rat Mesenteric Arteries

by Helga Helgadóttir, Teresa Tropea, Sveinbjörn Gizurarson and Maurizio Mandalà

Int. J. Mol. Sci. 2021, 22(18), 10162; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221810162 - 21 Sep 2021

Cited by 2 | Viewed by 2657

Abstract

Acetylsalicylic acid (aspirin) exhibits a broad range of activities, including analgesic, antipyretic, and antiplatelet properties. Recent clinical studies also recommend aspirin prophylaxis in women with a high risk of pre-eclampsia, a major complication of pregnancy characterized by hypertension. We investigated the effect of aspirin on mesenteric resistance arteries and found outdiscovered the molecular mechanism underlying this action. Aspirin (10⁻¹²–10⁻⁶ M) was tested on pregnant rat mesenteric resistance arteries by a pressurized arteriography. Aspirin was investigated in the presence of several inhibitors of: (a) nitric oxide synthase (L-NAME 2 × 10⁻⁴ M); (b) cyclooxygenase (Indomethacin, 10⁻⁵ M); (c) Ca²⁺-activated K⁺ channels (Kca): small conductance (SKca, Apamin, 10⁻⁷ M), intermediate conductance (IKca, TRAM34, 10⁻⁵ M), and big conductance (BKca, paxilline, 10⁻⁵ M); and (d) endothelial-derived hyperpolarizing factor (high KCl, 80 mM). Aspirin caused a concentration-dependent vasodilation. Aspirin-vasodilation was abolished by removal of endothelium or by high KCl. Furthermore, preincubation with either apamin plus TRAM-34 or paxillin significantly attenuated aspirin vasodilation (p < 0.05). For the first time, we showed that aspirin induced endothelium-dependent vasodilation in mesenteric resistance arteries through the endothelial-derived hyperpolarizing factor (EDHF) and calcium-activated potassium channels. By activating this molecular mechanism, aspirin may lower peripheral vascular resistance and be beneficial in pregnancies complicated by hypertension. Full article

(This article belongs to the Special Issue Molecular Vascular Physiology)

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12 pages, 2004 KiB

Open AccessArticle

Bisphenol a Interferes with Uterine Artery Features and Impairs Rat Feto-Placental Growth

by Laura Barberio, Luana Paulesu, Laura Canesi, Elena Grasselli and Maurizio Mandalà

Int. J. Mol. Sci. 2021, 22(13), 6912; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22136912 - 27 Jun 2021

Cited by 15 | Viewed by 2362

Abstract

Bisphenol A (BPA) is a widespread environmental contaminant, found in human fluids and tissues. Maternal BPA exposure is associated with alterations in pregnancy outcomes. Because maternal uterine circulation plays a crucial role in normal placenta and fetal growth, we hypothesized that BPA compromises the function of uterine arteries (UAs) and fetoplacental development. Female rats were orally administered with BPA (2.5, 25 and 250 µg/kg/day) or with its vehicle (ethanol) for 30 days before pregnancy and during the first 20 days of pregnancy. To compare the effect of BPA in the reproductive vs. systemic circulation, it was tested on UAs and mesenteric arteries (MAs). Arteries were isolated and examined by pressure myography. Moreover, fetuses and placentas were weighed to provide an index of reproductive performance. In UAs of BPA-treated rats, lumen diameter, acetylcholine-relaxation and expressions of endothelial nitric oxide synthase 3 (NOS3), estrogen receptor α (ERα) and peroxisome proliferator-activated receptor ɣ (PPARɣ) were reduced. Conversely, no changes were observed in MAs. BPA treatment also reduced placental weights, while fetal weights were increased. For the first time, our results indicate that UAs represent a specific target of BPA during pregnancy and provide insight into the molecular mechanisms that underlie its negative effects on pregnancy outcomes. Full article

(This article belongs to the Special Issue Molecular Vascular Physiology)

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12 pages, 1889 KiB

Open AccessArticle

Molecular Pathomechanisms of Impaired Flow-Induced Constriction of Cerebral Arteries Following Traumatic Brain Injury: A Potential Impact on Cerebral Autoregulation

by Annamaria Szenasi, Krisztina Amrein, Endre Czeiter, Nikolett Szarka, Peter Toth and Akos Koller

Int. J. Mol. Sci. 2021, 22(12), 6624; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22126624 - 21 Jun 2021

Cited by 5 | Viewed by 2833

Abstract

(1) Background: Traumatic brain injury (TBI) frequently occurs worldwide, resulting in high morbidity and mortality. Here, we hypothesized that TBI impairs an autoregulatory mechanism, namely the flow-induced constriction of isolated rat middle cerebral arteries (MCAs). (2) Methods: TBI was induced in anaesthetized rats by weight drop model, and then MCAs were isolated and transferred into a pressure-flow chamber. The internal diameter was measured by a video-microscopy. (3) Results: In MCAs from intact rats, increases in flow and pressure + flow elicited constrictions (−26 ± 1.9 µm and −52 ± 2.8 µm, p < 0.05), which were significantly reduced after TBI or in the presence of thromboxane-prostanoid (TP receptor) antagonist SQ 29,548. Flow-induced constrictions were significantly reduced by HET0016, inhibitor of cytochrome P450 4A (CYP450 4A). Arachidonic acid, (AA, 10⁻⁷ M), and CYP-450 4A metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) elicited constrictions of intact MCA (−26 ± 2.3% and −31 ± 3.6%), which were significantly reduced after TBI (to 11 ± 1.3% and −16 ±2.5%). The TP receptor agonist U46619 (10⁻⁷ M) elicited substantial constrictions of MCA from intact rats (−21 ± 3.3%), which were also significantly reduced, after TBI (to −16 ± 2.4%). (4) Conclusions: Flow-induced constrictor response of MCA is impaired by traumatic brain injury, likely due to the reduced ability of cytochrome P450 4A to convert arachidonic acid to constrictor prostaglandins and the mitigated sensitivity of thromboxane-prostanoid receptors. Full article

(This article belongs to the Special Issue Molecular Vascular Physiology)

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10 pages, 1279 KiB

Open AccessArticle

Enhanced Nitrite-Mediated Relaxation of Placental Blood Vessels Exposed to Hypoxia Is Preserved in Pregnancies Complicated by Fetal Growth Restriction

by Teresa Tropea, Carina Nihlen, Eddie Weitzberg, Jon O. Lundberg, Mark Wareing, Susan L. Greenwood, Colin P. Sibley and Elizabeth C. Cottrell

Int. J. Mol. Sci. 2021, 22(9), 4500; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094500 - 26 Apr 2021

Cited by 2 | Viewed by 2302

Abstract

Nitric oxide (NO) is essential in the control of fetoplacental vascular tone, maintaining a high flow−low resistance circulation that favors oxygen and nutrient delivery to the fetus. Reduced fetoplacental blood flow is associated with pregnancy complications and is one of the major causes of fetal growth restriction (FGR). The reduction of dietary nitrate to nitrite and subsequently NO may provide an alternative source of NO in vivo. We have previously shown that nitrite induces vasorelaxation in placental blood vessels from normal pregnancies, and that this effect is enhanced under conditions of hypoxia. Herein, we aimed to determine whether nitrite could also act as a vasodilator in FGR. Using wire myography, vasorelaxant effects of nitrite were assessed on pre-constricted chorionic plate arteries (CPAs) and veins (CPVs) from normal and FGR pregnancies under normoxic and hypoxic conditions. Responses to the NO donor, sodium nitroprusside (SNP), were assessed in parallel. Nitrate and nitrite concentrations were measured in fetal plasma. Hypoxia significantly enhanced vasorelaxation to nitrite in FGR CPAs (p < 0.001), and in both normal (p < 0.001) and FGR (p < 0.01) CPVs. Vasorelaxation to SNP was also potentiated by hypoxia in both normal (p < 0.0001) and FGR (p < 0.01) CPVs. However, compared to vessels from normal pregnancies, CPVs from FGR pregnancies showed significantly lower reactivity to SNP (p < 0.01). Fetal plasma concentrations of nitrate and nitrite were not different between normal and FGR pregnancies. Together, these data show that nitrite-mediated vasorelaxation is preserved in FGR, suggesting that interventions targeting this pathway have the potential to improve fetoplacental blood flow in FGR pregnancies. Full article

(This article belongs to the Special Issue Molecular Vascular Physiology)

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15 pages, 2705 KiB

Open AccessArticle

Hypoxic Conditions Promote Rhythmic Contractile Oscillations Mediated by Voltage-Gated Sodium Channels Activation in Human Arteries

by Anne Virsolvy, Aurélie Fort, Lucie Erceau, Azzouz Charrabi, Maurice Hayot, Franck Aimond and Sylvain Richard

Int. J. Mol. Sci. 2021, 22(5), 2570; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22052570 - 04 Mar 2021

Cited by 5 | Viewed by 1759

Abstract

Arterial smooth muscle exhibits rhythmic oscillatory contractions called vasomotion and believed to be a protective mechanism against tissue hypoperfusion or hypoxia. Oscillations of vascular tone depend on voltage and follow oscillations of the membrane potential. Voltage-gated sodium channels (Na_v), responsible for the initiation and propagation of action potentials in excitable cells, have also been evidenced both in animal and human vascular smooth muscle cells (SMCs). For example, they contribute to arterial contraction in rats, but their physiopathological relevance has not been established in human vessels. In the present study, we investigated the functional role of Na_v in the human artery. Experiments were performed on human uterine arteries obtained after hysterectomy and on SMCs dissociated from these arteries. In SMCs, we recorded a tetrodotoxin (TTX)-sensitive and fast inactivating voltage-dependent I_Na current. Various Na_v genes, encoding α-subunit isoforms sensitive (Na_v 1.2; 1.3; 1.7) and resistant (Na_v 1.5) to TTX, were detected both in arterial tissue and in SMCs. Na_v channels immunostaining showed uniform distribution in SMCs and endothelial cells. On arterial tissue, we recorded variations of isometric tension, ex vivo, in response to various agonists and antagonists. In arterial rings placed under hypoxic conditions, the depolarizing agent KCl and veratridine, a specific Na_v channels agonist, both induced a sustained contraction overlaid with rhythmic oscillations of tension. After suppression of sympathetic control either by blocking the release of catecholamine or by antagonizing the target adrenergic response, rhythmic activity persisted while the sustained contraction was abolished. This rhythmic activity of the arteries was suppressed by TTX but, in contrast, only attenuated by antagonists of calcium channels, Na⁺/Ca²⁺ exchanger, Na⁺/K⁺-ATPase and the cardiac Na_v channel. These results highlight the role of Na_v as a novel key element in the vasomotion of human arteries. Hypoxia promotes activation of Na_v channels involved in the initiation of rhythmic oscillatory contractile activity. Full article

(This article belongs to the Special Issue Molecular Vascular Physiology)

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Review

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16 pages, 660 KiB

Open AccessReview

Exosomes as Intercellular Messengers in Hypertension

by Olufunke Omolola Arishe, Fernanda Priviero, Stephanie A. Wilczynski and R. Clinton Webb

Int. J. Mol. Sci. 2021, 22(21), 11685; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222111685 - 28 Oct 2021

Cited by 14 | Viewed by 3248

Abstract

People living with hypertension have a higher risk of developing heart diseases, and hypertension remains a top cause of mortality. In hypertension, some detrimental changes occur in the arterial wall, which include physiological and biochemical changes. Furthermore, this disease is characterized by turbulent blood flow, increased fluid shear stress, remodeling of the blood vessels, and endothelial dysfunction. As a complex disease, hypertension is thought to be caused by an array of factors, its etiology consisting of both environmental and genetic factors. The Mosaic Theory of hypertension states that many factors, including genetics, environment, adaptive, neural, mechanical, and hormonal perturbations are intertwined, leading to increases in blood pressure. Long-term efforts by several investigators have provided invaluable insight into the physiological mechanisms responsible for the pathogenesis of hypertension, and these include increased activity of the sympathetic nervous system, overactivation of the renin–angiotensin–aldosterone system (RAAS), dysfunction of the vascular endothelium, impaired platelet function, thrombogenesis, vascular smooth muscle and cardiac hypertrophy, and altered angiogenesis. Exosomes are extracellular vesicles released by all cells and carry nucleic acids, proteins, lipids, and metabolites into the extracellular environment. They play a role in intercellular communication and are involved in the pathophysiology of diseases. Since the discovery of exosomes in the 1980s, numerous studies have been carried out to understand the biogenesis, composition, and function of exosomes. In this review, we will discuss the role of exosomes as intercellular messengers in hypertension. Full article

(This article belongs to the Special Issue Molecular Vascular Physiology)

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18 pages, 1889 KiB

Open AccessReview

Hypoxia Pathway Proteins and Their Impact on the Blood Vasculature

by Diego Rodriguez, Deepika Watts, Diana Gaete, Sundary Sormendi and Ben Wielockx

Int. J. Mol. Sci. 2021, 22(17), 9191; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22179191 - 25 Aug 2021

Cited by 24 | Viewed by 5334

Abstract

Every cell in the body requires oxygen for its functioning, in virtually every animal, and a tightly regulated system that balances oxygen supply and demand is therefore fundamental. The vascular network is one of the first systems to sense oxygen, and deprived oxygen (hypoxia) conditions automatically lead to a cascade of cellular signals that serve to circumvent the negative effects of hypoxia, such as angiogenesis associated with inflammation, tumor development, or vascular disorders. This vascular signaling is driven by central transcription factors, namely the hypoxia inducible factors (HIFs), which determine the expression of a growing number of genes in endothelial cells and pericytes. HIF functions are tightly regulated by oxygen sensors known as the HIF-prolyl hydroxylase domain proteins (PHDs), which are enzymes that hydroxylate HIFs for eventual proteasomal degradation. HIFs, as well as PHDs, represent attractive therapeutic targets under various pathological settings, including those involving vascular (dys)function. We focus on the characteristics and mechanisms by which vascular cells respond to hypoxia under a variety of conditions. Full article

(This article belongs to the Special Issue Molecular Vascular Physiology)

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21 pages, 24435 KiB

Open AccessReview

Targeting the Angiotensin II Type 1 Receptor in Cerebrovascular Diseases: Biased Signaling Raises New Hopes

by Céline Delaitre, Michel Boisbrun, Sandra Lecat and François Dupuis

Int. J. Mol. Sci. 2021, 22(13), 6738; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22136738 - 23 Jun 2021

Cited by 4 | Viewed by 3949

Abstract

The physiological and pathophysiological relevance of the angiotensin II type 1 (AT₁) G protein-coupled receptor no longer needs to be proven in the cardiovascular system. The renin–angiotensin system and the AT₁ receptor are the targets of several classes of therapeutics (such as angiotensin converting enzyme inhibitors or angiotensin receptor blockers, ARBs) used as first-line treatments in cardiovascular diseases. The importance of AT₁ in the regulation of the cerebrovascular system is also acknowledged. However, despite numerous beneficial effects in preclinical experiments, ARBs do not induce satisfactory curative results in clinical stroke studies. A better understanding of AT₁ signaling and the development of biased AT₁ agonists, able to selectively activate the β-arrestin transduction pathway rather than the G_q pathway, have led to new therapeutic strategies to target detrimental effects of AT₁ activation. In this paper, we review the involvement of AT₁ in cerebrovascular diseases as well as recent advances in the understanding of its molecular dynamics and biased or non-biased signaling. We also describe why these alternative signaling pathways induced by β-arrestin biased AT₁ agonists could be considered as new therapeutic avenues for cerebrovascular diseases. Full article

(This article belongs to the Special Issue Molecular Vascular Physiology)

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27 pages, 1960 KiB

Open AccessReview

The Protective Effects of the Autophagic and Lysosomal Machinery in Vascular and Valvular Calcification: A Systematic Review

by Cédric H. G. Neutel, Jhana O. Hendrickx, Wim Martinet, Guido R. Y. De Meyer and Pieter-Jan Guns

Int. J. Mol. Sci. 2020, 21(23), 8933; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21238933 - 25 Nov 2020

Cited by 8 | Viewed by 4268

Abstract

Background: Autophagy is a highly conserved catabolic homeostatic process, crucial for cell survival. It has been shown that autophagy can modulate different cardiovascular pathologies, including vascular calcification (VCN). Objective: To assess how modulation of autophagy, either through induction or inhibition, affects vascular and valvular calcification and to determine the therapeutic applicability of inducing autophagy. Data sources: A systematic review of English language articles using MEDLINE/PubMed, Web of Science (WoS) and the Cochrane library. The search terms included autophagy, autolysosome, mitophagy, endoplasmic reticulum (ER)-phagy, lysosomal, calcification and calcinosis. Study characteristics: Thirty-seven articles were selected based on pre-defined eligibility criteria. Thirty-three studies (89%) studied vascular smooth muscle cell (VSMC) calcification of which 27 (82%) studies investigated autophagy and six (18%) studies lysosomal function in VCN. Four studies (11%) studied aortic valve calcification (AVCN). Thirty-four studies were published in the time period 2015–2020 (92%). Conclusion: There is compelling evidence that both autophagy and lysosomal function are critical regulators of VCN, which opens new perspectives for treatment strategies. However, there are still challenges to overcome, such as the development of more selective pharmacological agents and standardization of methods to measure autophagic flux. Full article

(This article belongs to the Special Issue Molecular Vascular Physiology)

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