Changes in extracellular matrix in subcutaneous small resistance arteries of patients with essential hypertension

Favero, Gaia; Paini, Anna; Ciuceis, Carolina De; Rodella, Luigi Fabrizio; Moretti, Enrico; Porteri, Enzo; Rossini, Claudia; Ministrini, Silvia; Solaini, Leonardo; Caletti, Stefano; Coschignano, Maria Antonietta; Brami, Valeria; Petelca, Alina; Nardin, Matteo; Valli, Ilenia; Tiberio, Guido A M; Bonomini, Francesca; Rosei, Claudia Agabiti; Portolani, Nazario; Rizzoni, Damiano

doi:10.1080/08037051.2018.1448256

Cited by 13 publications

(8 citation statements)

References 57 publications

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“…After washing, the sections were labelled with 488 anti-mouse or 546 anti-rabbit Alexa Fluor conjugated secondary antibodies (diluted 1:200; Invitrogen, Paisley, UK). Finally, the sections were counterstained with 4′-6-diamidino-2-phenylindole (DAPI) [58,59,60], mounted and observed with a fluorescent microscopy (i50 Eclipse, Nikon, Düsseldorf, Germany) at final magnification of 400× [61,62]. Sections without primary antibody and in the presence of isotype-matched IgG served as negative immunofluorescent controls.…”

Section: Methodsmentioning

confidence: 99%

Mitochondrial Dysfunction in Skeletal Muscle of a Fibromyalgia Model: The Potential Benefits of Melatonin

Favero

Bonomini

Franco

2019

IJMS

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Fibromyalgia syndrome (FMS) is considered a musculoskeletal disorder associated to other symptoms including chronic pain. Since the hypothesis of FMS etiogenesis is consistent with mitochondrial dysfunction and oxidative stress, we evaluated the pathophysiological correlation among these factors studying some proteins involved in the mitochondrial homeostasis. We focused our attention on the roles of peroxisome proliferator activated receptor gamma coactivator-1alpha (PGC-1α), mitofusin2 (Mfn2), and coenzyme Q10 (CoQ10) in reserpine-induced myalgic (RIM) rats that manifest fibromyalgia-like chronic pain symptoms. First, we underlined that RIM rats are a good model for studying the pathophysiology of FMS and moreover, we found that PGC-1α, Mfn2, and CoQ10 are involved in FMS. In fact, their expressions were reduced in gastrocnemius muscle determining an incorrect mitochondrial homeostasis. Today, none of the currently available drugs are fully effective against the symptoms of this disease and they, often, induce several adverse events; hence, many scientists have taken on the challenge of searching for non-pharmacological treatments. Another goal of this study was therefore the evaluation of the potential benefits of melatonin, an endogenous indoleamine having several functions including its potent capacity to induce antioxidant enzymes and to determine the protective or reparative mechanisms in the cells. We observed that melatonin supplementation significantly preserved all the studied parameters, counteracting oxidative stress in RIM rats and confirming that this indoleamine should be taken in consideration for improving health and/or counteract mitochondrial related diseases.

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Section: Methodsmentioning

confidence: 99%

Mitochondrial Dysfunction in Skeletal Muscle of a Fibromyalgia Model: The Potential Benefits of Melatonin

Favero

Bonomini

Franco

2019

IJMS

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“…Finally, the cells were counterstained with 4',6-diamidino-2-phenylindole (DAPI) [14–16]. The cell immunofluorescence assays were observed with a fluorescent microscope (i50 Eclipse, Nikon, Düsseldorf, Germany) as previously described by [17, 18]. The control for each immunofluorescence was performed by omitting the primary antibody and in the presence of isotype-matched total immunoglobulin G.…”

Section: Methodsmentioning

confidence: 99%

A carnosine analog with therapeutic potentials in the treatment of disorders related to oxidative stress

et al. 2019

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Interactive relationships among metabolism, mitochondrial dysfunction and inflammation at skeletal muscle level play a key role in the pathogenesis of disorders related to oxidative stress. Mitochondrial dysfunction and oxidative stress result in cellular energy deficiency, inflammation and cell death inducing a vicious cycle that promotes muscle wasting. The histidine-containing dipeptides, carnosine and anserine, are carbonyl scavengers whose cytoprotective contributions extend beyond the antioxidant defence, but the physiological meaning of these capacities is actually limited. In the present study, we compared and investigated the potential protective effects of three different histidine-containing dipeptides: carnosine, anserine and carnosinol, a carnosine-mimetic new compound, against oxidative stress induction in rat L6 skeletal muscle cells. The hydrogen peroxide induced-oxidative stress significantly altered cell morphology, induced apoptosis, oxidative stress and inflammation, decreased mitochondrial peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α)/sirtuin3 pathway and the antioxidant system. Notably, all three investigated dipeptides in the present study, with a different extent and in a concentration-dependent manner, reduced myotube oxidative stress, apoptosis and inflammation. The present study underlined that carnosinol, maintaining the safety condition of carnosine and anserine, was the more efficient studied dipeptide in the preservation of mitochondrial environment mediated by PGC-1α and sirtuin3 expression and thereby in the reduction of oxidative stress-related alterations in this in vitro skeletal muscle model. Furthermore, we observed that carnosinol’s antioxidant effects are not blocked inhibiting sirtuin3, but are maintained with almost the same extend, indicating its multiple capacities of reactive carbonyl species-scavenging and of mitochondrial modulation through PGC-1α. In conclusion, carnosinol retained and surpassed the efficacy of the well-known investigated histidine-containing dipeptides improving oxidative stress, inflammation and also cell metabolism and so becoming a greatly promising therapeutic carnosine derivate.

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Section: Small and Large Artery Remodeling And Functional Changesmentioning

confidence: 99%

“…Collagen seems to be increased in subcutaneous resistance arteries in patients with essential hypertension 8 ; fibronectin and TGF-β1 tunica media content is also increased, while laminin and emilin-1 content is decreased. 9 Integrins such as alpha-v integrin, tissue-type transglutaminase, metalloproteinases, and adhesion molecules may play a relevant role in the development of microvascular remodeling, possibly contributing to a loose anchoring of VSMC to ECM components. 5,7 Although changes in ECM may contribute to the increased microvascular stiffness, no or modest changes in the wall stressincremental elastic modulus relationship were found in previous studies, when hypertensive patients and normotensive controls were compared.…”

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confidence: 99%

Microcirculation and Macrocirculation in Hypertension: A Dangerous Cross-Link?

et al. 2022

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Microcirculation and macrocirculation are tightly interconnected into a dangerous cross-link in hypertension. Small artery damage includes functional (vasoconstriction, impaired vasodilatation) and structural abnormalities (mostly inward eutrophic remodeling). These abnormalities are major determinants of the increase in total peripheral resistance and mean blood pressure (BP) in primary hypertension, which in the long term induces large artery stiffening. In turn, large artery stiffening increases central systolic and pulse pressures, which are further augmented by wave reflection in response to the structural alterations in small resistance arteries. Finally, transmission of high BP and flow pulsatility to small resistance arteries further induces functional and structural abnormalities, thus leading to increased total peripheral resistance and mean BP, thus perpetuating the vicious circle. Hyperpulsatility, in addition to higher mean BP, exaggerates cardiac, brain, and kidney damages and leads to cardiovascular, cerebral, and renal complications. The dangerous cross-link between micro and macrocirculation can be reversed into a virtuous one by ACE (angiotensin-converting enzyme) inhibitors, sartans, and calcium channel blockers. These three pharmacological classes are more potent than β-blockers and diuretics for reducing arterial stiffness and small artery remodeling. The same ranking was observed for their effectiveness at reducing left ventricular hypertrophy, preserving glomerular filtration rate, and preventing dementia, suggesting that they can act beyond brachial BP reduction, by breaking the micro/macrocirculation vicious circle.

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Changes in extracellular matrix in subcutaneous small resistance arteries of patients with essential hypertension

Cited by 13 publications

References 57 publications

Mitochondrial Dysfunction in Skeletal Muscle of a Fibromyalgia Model: The Potential Benefits of Melatonin

Mitochondrial Dysfunction in Skeletal Muscle of a Fibromyalgia Model: The Potential Benefits of Melatonin

A carnosine analog with therapeutic potentials in the treatment of disorders related to oxidative stress

Microcirculation and Macrocirculation in Hypertension: A Dangerous Cross-Link?

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