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1. Cardiac involvement in creatine deficiency syndrome

Author

Del Franco, A, primary, Battini, R, additional, Kusmic, C, additional, Forini, F S, additional, L'Abbate, S, additional, Masotti, S, additional, Musetti, V, additional, Borrelli, C, additional, Barison, A, additional, Emdin, M, additional, and Vergaro, G, additional

Published
2022
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7. Autoantibody Recognition of COOH-Terminal Epitopes of GAD65 Marks the Risk for Insulin Requirement in Adult-Onset Diabetes Mellitus

Author

Falorni, Alberto, Gambelunghe, G., Forini, F., Kassi, G., Cosentino, A., Candeloro, P., Bolli, Geremia Brunetto, Brunetti, P., and Calcinaro, F.

Subjects
Adult, Male, Time Factors, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Iodide Peroxidase, Biochemistry, Epitopes, Endocrinology, Risk Factors, Humans, Hypoglycemic Agents, Insulin, Aged, Autoantibodies, C-Peptide, Glutamate Decarboxylase, Biochemistry (medical), Middle Aged, Isoenzymes, Cross-Sectional Studies, Diabetes Mellitus, Type 1, Italy, Female, Biomarkers, Follow-Up Studies
Abstract

Some type 2 diabetic subjects develop secondary failure to sulphonylurea treatment and require insulin therapy. To test the diagnostic sensitivity and specificity of epitopes of GAD65 autoantibodies (GAD65Ab) for insulin requirement, in patients with latent autoimmune diabetes of the adult, we studied 569 adult subjects with a clinical diagnosis of type 2 diabetes mellitus. All the patients had been initially treated with hypoglycemic agents and/or diet for at least 1 yr. The presence of GAD65Ab (61/569, 10.7%) depended on insulin therapy (P0.0001), low BMI (P0.0001), and low basal C-peptide (P = 0.01). The majority of GAD65Ab-positive subjects (47/61, 77%) had antibodies directed to both middle (GAD65-MAb) and COOH-terminal (GAD65-CAb) epitopes. However, GAD65-CAb were more frequent in insulin-treated subjects (92% of GAD65Ab+ individuals) than in subjects treated with hypoglycemic agents and/or diet (18.2% of GAD65Ab+ individuals), while the exclusive presence of GAD65-MAb was more frequent in subjects treated with hypoglycemic agents and/or diet (81.8% vs. 8%) (P0.0001). The presence of GAD65-CAb had a diagnostic specificity for insulin requirement as high as 99.4% (compared with 96.9% of GAD65Ab as measured in the traditional radiobinding assay) and identified a subgroup of patients with low BMI, low basal C-peptide values, and a need for insulin therapy. Subjects carrying only GAD65-MAb were phenotypically indistinguishable from GAD65Ab-negative patients. Patients positive for GAD65-M+CAb, but not those positive for GAD65-MAb only, showed an increased risk for thyroid autoimmunity, as revealed by the presence of thyroid peroxidase autoantibodies. Our study demonstrates that the use of epitope-specific antibody assays improves the diagnostic specificity of GAD65Ab, and that the presence of GAD65Ab binding to COOH-terminal epitopes is strongly associated with a need for insulin requirement.

Published
2000

8. Poster session 3Cell growth, differentiation and stem cells - Heart511The role of the endocannabinoid system in modelling muscular dystrophy cardiac disease with induced pluripotent stem cells.512An emerging role of T lymphocytes in cardiac regenerative processes in heart failure due to dilated cardiomyopathy513Canonical wnt signaling reverses the ‘aged/senescent’ human endogenous cardiac stem cell phenotype514Hippo signalling modulates survival of human induced pluripotent stem cell-derived cardiomyocytes515Biocompatibility of mesenchymal stem cells with a spider silk matrix and its potential use as scaffold for cardiac tissue regeneration516A snapshot of genome-wide transcription in human induced pluripotent stem cell-derived hepatocyte-like cells (iPSC-HLCs)517Can NOS/sGC/cGK1 pathway trigger the differentiation and maturation of mouse embryonic stem cells (ESCs)?518Introduction of external Ik1 to human-induced pluripotent stem cell-derived cardiomyocytes via Ik1-expressing HEK293519Cell therapy of the heart studied using adult myocardial slices in vitro520Enhancement of the paracrine potential of human adipose derived stem cells when cultured as spheroid bodies521Mechanosensitivity of cardiomyocyte progenitor cells: the strain response in 2D and 3D environments522The effect of the vascular-like network on the maturation of the human induced pluripotent stem cell derived cardiomyocytes.Transcriptional control and RNA species - Heart525Gene expression regulation in heart failure: from pathobiology to bioinformatics526Human transcriptome in idiopathic dilated cardiomyopathy - a novel high throughput screening527A high-throghput approach unveils putative miRNA-mediated mitochondria-targeted cardioprotective circuits activated by T3 in the post ischemia reperfusion setting528The effect of uraemia on the expression of miR-212/132 and the calcineurin pathway in the rat heartCytokines and cellular inflammation - Heart531Lack of growth differentiation factor 15 aggravates adverse cardiac remodeling upon pressure-overload in mice532Blocking heteromerization of platelet chemokines ccl5 and cxcl4 reduces inflammation and preserves heart function after myocardial infarction533Is there an association between low-dose aspirin use and clinical outcome in HFPEF? Implications of modulating monocyte function and inflammatory mediator release534N-terminal truncated intracellular matrix metalloproteinase-2 expression in diabetic heart.535Expression of CD39 and CD73 on peripheral T-cell subsets in calcific aortic stenosis536Mast cells in the atrial myocardium of patients with atrial fibrillation: a comparison with patients in sinus rhythm539Characteristics of the inflammatory response in patients with coronary artery disease and arterial hypertension540Pro-inflammatory cytokines as cardiovascular events predictors in rheumatoid arthritis and asymptomatic atherosclerosis541Characterization of FVB/N murinic bone marrow-derived macrophage polarization into M1 and M2 phenotypes542The biological expression and thoracic anterior pain syndromeSignal transduction - Heart545The association of heat shock protein 90 and TGFbeta receptor I is involved in collagen production during cardiac remodelling in aortic-banded mice546Loss of the inhibitory GalphaO protein in the rostral ventrolateral medulla of the brainstem leads to abnormalities in cardiovascular reflexes and altered ventricular excitablitiy547Selenoprotein P regulates pressure overload-induced cardiac remodeling548Study of adenylyl cyclase activity in erythrocyte membranes in patients with chronic heart failure549Direct thrombin inhibitors inhibit atrial myocardium hypertrophy in a rat model of heart failure and atrial remodeling550Tissue factor / FVIIa transactivates the IGF-1R by a Src-dependent phosphorylation of caveolin-1551Notch signaling is differently altered in endothelial and smooth muscle cells of ascending aortic aneurysm patients552Frizzled 5 expression is essential for endothelial proliferation and migration553Modulation of vascular function and ROS production by novel synthetic benzopyran analogues in diabetes mellitusExtracellular matrix and fibrosis - Heart556Cardiac fibroblasts as inflammatory supporter cells trigger cardiac inflammation in heart failure557A role for galectin-3 in calcific aortic valve stenosis558Omega-3 polyunsaturated fatty acids- can they decrease risk for ventricular fibrillation?559Serum levels of elastin derived peptides and circulating elastin-antielastin immune complexes in sera of patients with coronary artery disease560Endocardial fibroelastosis is secondary to hemodynamic alterations in the chick model of hypoplastic left heart syndrome561Dynamics of serum levels of matrix metalloproteinases in primary anterior STEMI patients564Deletion of the alpha-7 nicotinic acetylcholine receptor changes the vascular remodeling induced by transverse aortic constriction in mice.565Extracellular matrix remodelling in response to venous hypertension: proteomics of human varicose veinsIon channels, ion exchangers and cellular electrophysiology - Heart568Microtubule-associated protein RP/EB family member 1 modulates sodium channel trafficking and cardiac conduction569Investigation of electrophysiological abnormalities in a rabbit athlete's heart model570Upregulation of expression of multiple genes in the atrioventricular node of streptozotocin-induced diabetic rat571miR-1 as a regulator of sinoatrial rhythm in endurance training adaptation572Selective sodium-calcium exchanger inhibition reduces myocardial dysfunction associated with hypokalaemia and ventricular fibrillation573Effect of racemic and levo-methadone on action potential of human ventricular cardiomyocytes574Acute temperature effects on the chick embryonic heart functionVasculogenesis, angiogenesis and arteriogenesis577Clinical improvement and enhanced collateral vessel growth after monocyte transplantation in mice578The role of HIF-1 alpha, VEGF and obstructive sleep apnoea in the development of coronary collateral circulation579Initiating cardiac repair with a trans-coronary sinus catheter intervention in an ischemia/reperfusion porcine animal model580Early adaptation of pre-existing collaterals after acute arteriolar and venular microocclusion: an in vivo study in chick chorioallantoic membraneEndothelium583EDH-type responses to the activator of potassium KCa2.3 and KCa3.1 channels SKA-31 in the small mesenteric artery from spontaneously hypertensive rats584The peculiarities of endothelial dysfunction in patients with chronic renocardial syndrome585Endothelial dysfunction, atherosclerosis of the carotid arteries and level of leptin in patient with coronary heart disease in combination with hepatic steatosis depend from body mass index.586Role of non-coding RNAs in thoracic aortic aneurysm associated with bicuspid aortic valve587Cigarette smoke extract abrogates atheroprotective effects of high laminar flow on endothelial function588The prognostic value of anti-connective tissue antibodies in coronary heart disease and asymptomatic atherosclerosis589Novel potential properties of bioactive peptides from spanish dry-cured ham on the endothelium.Lipids592Intermediate density lipoprotein is associated with monocyte subset distribution in patients with stable atherosclerosis593The characteristics of dyslipidemia in rheumatoid arthritisAtherosclerosis596Macrophages differentiated in vitro are heterogeneous: morphological and functional profile in patients with coronary artery disease597Palmitoylethanolamide promotes anti-inflammatory phenotype of macrophages and attenuates plaque formation in ApoE-/- mice598Amiodarone versus esmolol in the perioperative period: an in vitro study of coronary artery bypass grafts599BMPRII signaling of fibrocytes, a mesenchymal progenitor cell population, is increased in STEMI and dyslipidemia600The characteristics of atherogenesis and systemic inflammation in rheumatoid arthritis601Role of adenosine-to-inosine RNA editing in human atherosclerosis602Presence of bacterial DNA in thrombus aspirates of patients with myocardial infarction603Novel E-selectin binding polymers reduce atherosclerotic lesions in ApoE(-/-) mice604Differential expression of the plasminogen receptor Plg-RKT in monocyte and macrophage subsets - possible functional consequences in atherogenesis605Apelin-13 treatment enhances the stability of atherosclerotic plaques606Mast cells are increased in the media of coronary lesions in patients with myocardial infarction and favor atherosclerotic plaque instability607Association of neutrophil to lymphocyte ratio with presence of isolated coronary artery ectasiaCalcium fluxes and excitation-contraction coupling610The coxsackie- and adenovirus receptor (CAR) regulates calcium homeostasis in the developing heart611HMW-AGEs application acutely reduces ICaL in adult cardiomyocytes612Measuring electrical conductibility of cardiac T-tubular systems613Postnatal development of cardiac excitation-contraction coupling in rats614Role of altered Ca2+ homeostasis during adverse cardiac remodeling after ischemia/reperfusion615Experimental study of sarcoplasmic reticulum dysfunction and energetic metabolism in failing myocardium associated with diabetes mellitusHibernation, stunning and preconditioning618Volatile anesthetic preconditioning attenuates ischemic-reperfusion injury in type II diabetic patients undergoing on-pump heart surgery619The effect of early and delayed phase of remote ischemic preconditioning on ischemia-reperfusion injury in the isolated hearts of healthy and diabetic rats620Post-conditioning with 1668-thioate leads to attenuation of the inflammatory response and remodeling with less fibrosis and better left ventricular function in a murine model of myocardial infarction621Maturation-related changes in response to ischemia-reperfusion injury and in effects of classical ischemic preconditioning and remote preconditioningMitochondria and energetics624Phase changes in myocardial mitochondrial respiration caused by hypoxic preconditioning or periodic hypoxic training625Desmin mutations depress mitochondrial metabolism626Methylene blue modulates mitochondrial function and monoamine oxidases-related ROS production in diabetic rat hearts627Doxorubicin modulates the real-time oxygen consumption rate of freshly isolated adult rat and human ventricular cardiomyocytesCardiomyopathies and fibrosis630Effects of genetic or pharmacologic inhibition of the ubiquitin/proteasome system on myocardial proteostasis and cardiac function631Suppression of Wnt signalling in a desmoglein-2 transgenic mouse model for arrhythmogenic cardiomyopathy632Cold-induced cardiac hypertrophy is reversed after thermo-neutral deacclimatization633CD45 is a sensitive marker to diagnose lymphocytic myocarditis in endomyocardial biopsies of living patients and in autopsies634Atrial epicardial adipose tissue derives from epicardial progenitors635Caloric restriction ameliorates cardiac function, sympathetic cardiac innervation and beta-adrenergic receptor signaling in an experimental model of post-ischemic heart failure636High fat diet improves cardiac remodelling and function after extensive myocardial infarction in mice637Epigenetic therapy reduces cardiac hypertrophy in murine models of heart failure638Imbalance of the VHL/HIF signaling in WT1+ Epicardial Progenitors results in coronary vascular defects, fibrosis and cardiac hypertrophy639Diastolic dysfunction is the first stage of the developing heart failure640Colchicine aggravates coxsackievirus B3 infection in miceArterial and pulmonary hypertension642Osteopontin as a marker of pulmonary hypertension in patients with coronary heart disease combined with chronic obstructive pulmonary disease643Myocardial dynamic stiffness is increased in experimental pulmonary hypertension partly due to incomplete relaxation644Hypotensive effect of quercetin is possibly mediated by down-regulation of immunotroteasome subunits in aorta of spontaneously hypertensive rats645Urocortin-2 improves right ventricular function and attenuates experimental pulmonary arterial hypertension646A preclinical evaluation of the anti-hypertensive properties of an aqueous extract of Agathosma (Buchu)Biomarkers648The adiponectin level in hypertensive females with rheumatoid arthritis and its relationship with subclinical atherosclerosis649Markers for identification of renal dysfunction in the patients with chronic heart failure650cardio-hepatic syndromes in chronic heart failure: North Africa profile651To study other biomarkers that assess during myocardial infarction652Interconnections of apelin levels with parameters of lipid metabolism in hypertension patients653Plasma proteomics in hypertension: prediction and follow-up of albuminuria during chronic renin-angiotensin system suppression654Soluble RAGE levels in plasma of patients with cerebrovascular events

Author

Gowran, A, primary, Kulikova, T, primary, Lewis, FC, primary, Foldes, G, primary, Fuentes, L, primary, Viiri, LE, primary, Spinelli, V, primary, Costa, A, primary, Perbellini, F, primary, Sid-Otmane, C, primary, Bax, NAM, primary, Pekkanen-Mattila, M, primary, Schiano, C, primary, Chaloupka, A, primary, Forini, F, primary, Sarkozy, M, primary, De Jager, SCA, primary, Vajen, T, primary, Glezeva, N, primary, Lee, H W, primary, Golovkin, A, primary, Kucera, T, primary, Musikhina, NA, primary, Korzhenkov, NP, primary, Santuchi, M DE C, primary, Munteanu, D, primary, Garcia, RG, primary, Ang, R, primary, Usui, S, primary, Kamilova, U, primary, Jumeau, C, primary, Aberg, M, primary, Kostina, DA, primary, Brandt, MM, primary, Muntean, D, primary, Lindner, D, primary, Sadaba, R, primary, Bacova, B, primary, Nikolov, A, primary, Sedmera, D, primary, Ryabov, V, primary, Neto, FP, primary, Lynch, M, primary, Portero, V, primary, Kui, P, primary, Howarth, FC, primary, Gualdoni, A, primary, Prorok, J, primary, Diolaiuti, L, primary, Vostarek, F, primary, Wagner, M, primary, Abela, MA, primary, Nebert, C, primary, Xiang, W, primary, Kloza, M, primary, Maslenko, A, primary, Grechanyk, M, primary, Bhattachariya, A, primary, Morawietz, H, primary, Babaeva, AR, primary, Martinez Sanchez, SM, primary, Krychtiuk, KA, primary, Starodubova, J, primary, Fiorelli, S, primary, Rinne, P, primary, Ozkaramanli Gur, D, primary, Hofbauer, T, primary, Stellos, K, primary, Pinon, P, primary, Tsoref, O, primary, Thaler, B, primary, Fraga-Silva, RA, primary, Fuijkschot, WW, primary, Shaaban, MNS, primary, Matthaeus, C, primary, Deluyker, D, primary, Scardigli, M, primary, Zahradnikova, A, primary, Dominguez, A, primary, Kondrat'eva, D, primary, Sosorburam, T, primary, Murarikova, M, primary, Duerr, GD, primary, Griecsova, L, primary, Portnichenko, VI, primary, Smolina, N, primary, Duicu, OANA M, primary, Elder, JM, primary, Zaglia, T, primary, Lorenzon, A, primary, Ruperez, C, primary, Woudstra, L, primary, Suffee, N, primary, De Lucia, C, primary, Russell-Hallinan, A, primary, Menendez-Montes, I, primary, Kapelko, VI, primary, Emmens, RW, primary, Hetman, O, primary, Van Der Laarse, WJ, primary, Goncharov, S, primary, Adao, R, primary, Huisamen, B, primary, Sirenko, O, primary, Nassiri, I, primary, Tserendavaa, SUMIYA, primary, Yushko, K, primary, Baldan Martin, M, primary, Falcone, C, primary, Vigorelli, V, additional, Nigro, P, additional, Pompilio, G, additional, Stepanova, O, additional, Valikhov, M, additional, Samko, A, additional, Masenko, V, additional, Tereschenko, S, additional, Teoh, T, additional, Domenjo-Vila, E, additional, Theologou, T, additional, Field, M, additional, Awad, W, additional, Yasin, M, additional, Nadal-Ginard, B, additional, Ellison-Hughes, GM, additional, Hellen, N, additional, Vittay, O, additional, Harding, SE, additional, Gomez-Cid, L, additional, Fernandez-Santos, ME, additional, Suarez-Sancho, S, additional, Plasencia, V, additional, Climent, A, additional, Sanz-Ruiz, R, additional, Hedhammar, M, additional, Atienza, F, additional, Fernandez-Aviles, F, additional, Kiamehr, M, additional, Oittinen, M, additional, Viiri, KM, additional, Kaikkonen, M, additional, Aalto-Setala, K, additional, Diolaiuti, L, additional, Laurino, A, additional, Sartiani, L, additional, Vona, A, additional, Zanardelli, M, additional, Cerbai, E, additional, Failli, P, additional, Hortigon-Vinagre, MP, additional, Van Der Heyden, M, additional, Burton, FL, additional, Smith, GL, additional, Watson, S, additional, Scigliano, M, additional, Tkach, S, additional, Alayoubi, S, additional, Terracciano, CM, additional, Ly, HQ, additional, Mauretti, A, additional, Van Marion, MH, additional, Van Turnhout, MC, additional, Van Der Schaft, DWJ, additional, Sahlgren, CM, additional, Goumans, MJ, additional, Bouten, CVC, additional, Vuorenpaa, H, additional, Penttinen, K, additional, Sarkanen, R, additional, Ylikomi, T, additional, Heinonen, T, additional, Grimaldi, V, additional, Aprile, M, additional, Esposito, R, additional, Maiello, C, additional, Soricelli, A, additional, Colantuoni, V, additional, Costa, V, additional, Ciccodicola, A, additional, Napoli, C, additional, Rowe, GC, additional, Johnson, K, additional, Arany, ZP, additional, Del Monte, F, additional, D'aurizio, R, additional, Kusmic, C, additional, Nicolini, G, additional, Baumgart, M, additional, Groth, M, additional, Ucciferri, N, additional, Iervasi, G, additional, Pitto, L, additional, Pipicz, M, additional, Gaspar, R, additional, Siska, A, additional, Foldesi, I, additional, Kiss, K, additional, Bencsik, P, additional, Thum, T, additional, Batkai, S, additional, Csont, T, additional, Haan, JJ, additional, Bosch, L, additional, Brans, MAD, additional, Van De Weg, SM, additional, Deddens, JC, additional, Lee, SJ, additional, Sluijter, JPG, additional, Pasterkamp, G, additional, Werner, I, additional, Projahn, D, additional, Staudt, M, additional, Curaj, A, additional, Soenmez, TT, additional, Simsekyilmaz, S, additional, Hackeng, TM, additional, Von Hundelshausen, P, additional, Koenen, RR, additional, Weber, C, additional, Liehn, EA, additional, Santos-Martinez, M, additional, Medina, C, additional, Watson, C, additional, Mcdonald, K, additional, Gilmer, J, additional, Ledwidge, M, additional, Song, SH, additional, Lee, MY, additional, Park, MH, additional, Choi, JC, additional, Ahn, JH, additional, Park, JS, additional, Oh, JH, additional, Choi, JH, additional, Lee, HC, additional, Cha, KS, additional, Hong, TJ, additional, Kudryavtsev, I, additional, Serebryakova, M, additional, Malashicheva, A, additional, Shishkova, A, additional, Zhiduleva, E, additional, Moiseeva, O, additional, Durisova, M, additional, Blaha, M, additional, Melenovsky, V, additional, Pirk, J, additional, Kautzner, J, additional, Petelina, TI, additional, Gapon, LI, additional, Gorbatenko, EA, additional, Potolinskaya, YV, additional, Arkhipova, EV, additional, Solodenkova, KS, additional, Osadchuk, MA, additional, Dutra, MF, additional, Oliveira, FCB, additional, Silva, MM, additional, Passos-Silva, DG, additional, Goncalves, R, additional, Santos, RAS, additional, Da Silva, RF, additional, Gavrilescu, CM, additional, Paraschiv, CM, additional, Manea, P, additional, Strat, LC, additional, Gomez, JMG, additional, Merino, D, additional, Hurle, MA, additional, Nistal, JF, additional, Aires, A, additional, Cortajarena, AL, additional, Villar, AV, additional, Abramowitz, J, additional, Birnbaumer, L, additional, Gourine, AV, additional, Tinker, A, additional, Takamura, M, additional, Takashima, S, additional, Inoue, O, additional, Misu, H, additional, Takamura, T, additional, Kaneko, S, additional, Alieva, TOHIRA, additional, Mougenot, N, additional, Dufilho, M, additional, Hatem, S, additional, Siegbahn, A, additional, Kostina, AS, additional, Uspensky, VE, additional, Moiseeva, OM, additional, Kostareva, AA, additional, Malashicheva, AB, additional, Van Dijk, CGM, additional, Chrifi, I, additional, Verhaar, MC, additional, Duncker, DJ, additional, Cheng, C, additional, Sturza, A, additional, Petrus, A, additional, Duicu, O, additional, Kiss, L, additional, Danila, M, additional, Baczko, I, additional, Jost, N, additional, Gotzhein, F, additional, Schon, J, additional, Schwarzl, M, additional, Hinrichs, S, additional, Blankenberg, S, additional, Volker, U, additional, Hammer, E, additional, Westermann, D, additional, Martinez-Martinez, E, additional, Arrieta, V, additional, Fernandez-Celis, A, additional, Jimenez-Alfaro, L, additional, Melero, A, additional, Alvarez-Asiain, V, additional, Cachofeiro, V, additional, Lopez-Andres, N, additional, Tribulova, N, additional, Wallukat, G, additional, Knezl, V, additional, Radosinska, J, additional, Barancik, M, additional, Tsinlikov, I, additional, Tsinlikova, I, additional, Nicoloff, G, additional, Blazhev, A, additional, Pesevski, Z, additional, Kvasilova, A, additional, Stopkova, T, additional, Eckhardt, A, additional, Buffinton, C M, additional, Nanka, O, additional, Kercheva, M, additional, Suslova, T, additional, Gusakova, A, additional, Ryabova, T, additional, Markov, V, additional, Karpov, R, additional, Seemann, H, additional, Alcantara, TC, additional, Santuchi, M DE C, additional, Fonseca, SG, additional, Barallobre-Barreiro, J, additional, Oklu, R, additional, Fava, M, additional, Baig, F, additional, Yin, X, additional, Albadawi, H, additional, Jahangiri, M, additional, Stoughton, J, additional, Mayr, M, additional, Podliesna, SP, additional, Veerman, CCV, additional, Verkerk, AOV, additional, Klerk, MK, additional, Lodder, EML, additional, Mengarelli, IM, additional, Bezzina, CRB, additional, Remme, CAR, additional, Takacs, H, additional, Polyak, A, additional, Morvay, N, additional, Lepran, I, additional, Tiszlavicz, L, additional, Nagy, N, additional, Ordog, B, additional, Farkas, A, additional, Forster, T, additional, Varro, A, additional, Farkas, AS, additional, Jayaprakash, P, additional, Parekh, K, additional, Ferdous, Z, additional, Oz, M, additional, Dobrzynski, H, additional, Adrian, TE, additional, Landi, S, additional, Bonzanni, M, additional, D'souza, A, additional, Boyett, M, additional, Bucchi, A, additional, Baruscotti, M, additional, Difrancesco, D, additional, Barbuti, A, additional, Kui, P, additional, Oravecz, K, additional, Hezso, T, additional, Levijoki, J, additional, Pollesello, P, additional, Koskelainen, T, additional, Otsomaa, L, additional, Farkas, A S, additional, Papp, JGY, additional, Toth, A, additional, Acsai, K, additional, Dini, L, additional, Mazzoni, L, additional, Mugelli, A, additional, Svatunkova, J, additional, Sedmera, D, additional, Deffge, C, additional, Baer, C, additional, Weinert, S, additional, Braun-Dullaeus, RC, additional, Herold, J, additional, Cassar, AC, additional, Zahra, GZ, additional, Pllaha, EP, additional, Dingli, PD, additional, Montefort, SM, additional, Xuereb, RGX, additional, Aschacher, T, additional, Messner, B, additional, Eichmair, E, additional, Mohl, W, additional, Reglin, B, additional, Rong, W, additional, Nitzsche, B, additional, Maibier, M, additional, Guimaraes, P, additional, Ruggeri, A, additional, Secomb, TW, additional, Pries, AR, additional, Baranowska-Kuczko, M, additional, Karpinska, O, additional, Kusaczuk, M, additional, Malinowska, B, additional, Kozlowska, H, additional, Demikhova, N, additional, Vynnychenko, L, additional, Prykhodko, O, additional, Grechanyk, N, additional, Kuryata, A, additional, Cottrill, KA, additional, Du, L, additional, Bjorck, HM, additional, Maleki, S, additional, Franco-Cereceda, A, additional, Chan, SY, additional, Eriksson, P, additional, Giebe, S, additional, Cockcroft, N, additional, Hewitt, K, additional, Brux, M, additional, Brunssen, C, additional, Tarasov, AA, additional, Davidov, SI, additional, Reznikova, EA, additional, Tapia Abellan, A, additional, Angosto Bazarra, D, additional, Pelegrin Vivancos, P, additional, Montoro Garcia, S, additional, Kastl, SP, additional, Pongratz, T, additional, Goliasch, G, additional, Gaspar, L, additional, Maurer, G, additional, Huber, K, additional, Dostal, E, additional, Pfaffenberger, S, additional, Oravec, S, additional, Wojta, J, additional, Speidl, WS, additional, Osipova, I, additional, Sopotova, I, additional, Eligini, S, additional, Cosentino, N, additional, Marenzi, G, additional, Tremoli, E, additional, Rami, M, additional, Ring, L, additional, Steffens, S, additional, Gur, O, additional, Gurkan, S, additional, Mangold, A, additional, Scherz, T, additional, Panzenboeck, A, additional, Staier, N, additional, Heidari, H, additional, Mueller, J, additional, Lang, IM, additional, Gatsiou, A, additional, Stamatelopoulos, K, additional, Perisic, L, additional, John, D, additional, Lunella, FF, additional, Hedin, U, additional, Zeiher, A, additional, Dimmeler, S, additional, Nunez, L, additional, Moure, R, additional, Marron-Linares, G, additional, Flores, X, additional, Aldama, G, additional, Salgado, J, additional, Calvino, R, additional, Tomas, M, additional, Bou, G, additional, Vazquez, N, additional, Hermida-Prieto, M, additional, Vazquez-Rodriguez, JM, additional, Amit, U, additional, Landa, N, additional, Kain, D, additional, Tyomkin, D, additional, David, A, additional, Leor, J, additional, Hohensinner, PJ, additional, Baumgartner, J, additional, Krychtiuk, KA, additional, Baik, N, additional, Miles, LA, additional, Seeman, H, additional, Montecucco, F, additional, Da Silva, AR, additional, Costa-Fraga, FP, additional, Anguenot, L, additional, Mach, FP, additional, Stergiopulos, N, additional, Kupreishvili, K, additional, Vonk, ABA, additional, Smulders, YM, additional, Van Hinsbergh, VWM, additional, Stooker, W, additional, Niessen, HWM, additional, Krijnen, PAJ, additional, Ashmawy, MM, additional, Salama, MA, additional, Elamrosy, MZ, additional, Juettner, R, additional, Rathjen, F G, additional, Bito, V, additional, Crocini, C, additional, Ferrantini, C, additional, Gabbrielli, T, additional, Silvestri, L, additional, Coppini, R, additional, Tesi, C, additional, Poggesi, C, additional, Pavone, FS, additional, Sacconi, L, additional, Mackova, K, additional, Zahradnik, I, additional, Zahradnikova, A, additional, Diaz, I, additional, Sanchez De Rojas De Pedro, E, additional, Hmadcha, K, additional, Calderon Sanchez, E, additional, Benitah, JP, additional, Gomez, AM, additional, Smani, T, additional, Ordonez, A, additional, Afanasiev, SA, additional, Egorova, MV, additional, Popov, SV, additional, Wu Qing, P, additional, Cheng, X, additional, Carnicka, S, additional, Pancza, D, additional, Jasova, M, additional, Kancirova, I, additional, Ferko, M, additional, Ravingerova, T, additional, Wu, S, additional, Schneider, M, additional, Marggraf, V, additional, Verfuerth, L, additional, Frede, S, additional, Boehm, O, additional, Dewald, O, 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Tserendavaa, SUMIYA, additional, Enkhtaivan, ODKHUU, additional, Shagdar, ZORIGO, additional, Malchinkhuu, MUNKHZ, additional, Malchinkhuu, MUNLHZ, additional, Koval, S, additional, Starchenko, T, additional, Mourino-Alvarez, L, additional, Gonzalez-Calero, L, additional, Sastre-Oliva, T, additional, Lopez, JA, additional, Vazquez, J, additional, Alvarez-Llamas, G, additional, Ruilope, LUIS M, additional, De La Cuesta, F, additional, Barderas, MG, additional, Bozzini, S, additional, D'angelo, A, additional, and Pelissero, G, additional

Published
2016
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9. New Insights into Mechanisms of Cardioprotection Mediated by Thyroid Hormones

Author

Nicolini, G., Pitto, L., Kusmic, C., Balzan, S., Sabatino, L., Iervasi, G., and Forini, F.

Subjects
Article Subject
Abstract

Heart failure represents the final common outcome in cardiovascular diseases. Despite significant therapeutic advances, morbidity and mortality of heart failure remain unacceptably high. Heart failure is preceded and sustained by a process of structural remodeling of the entire cardiac tissue architecture. Prevention or limitation of cardiac remodeling in the early stages of the process is a crucial step in order to ameliorate patient prognosis. Acquisition of novel pathophysiological mechanisms of cardiac remodeling is therefore required to develop more efficacious therapeutic strategies. Among all neuroendocrine systems, thyroid hormone seems to play a major homeostatic role in cardiovascular system. In these years, accumulating evidence shows that the “low triiodothyronine” syndrome is a strong prognostic, independent predictor of death in patients affected by both acute and chronic heart disease. In experimental models of cardiac hypertrophy or myocardial infarction, alterations in the thyroid hormone signaling, concerning cardiac mitochondrion, cardiac interstitium, and vasculature, have been suggested to be related to heart dysfunction. The aim of this brief paper is to highlight new developments in understanding the cardioprotective role of thyroid hormone in reverting regulatory networks involved in adverse cardiac remodeling. Furthermore, new recent advances on the role of specific miRNAs in thyroid hormone regulation at mitochondrion and interstitial level are also discussed.

Published
2013
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35. Effects of tetraiodothyronine and triiodothyronine on hamster cheek pouch microcirculation

Author

Fs Forini, Giorgio Iervasi, P.L. Marchiafava, Dominga Lapi, Antonio Colantuoni, Colantuoni, Antonio, Marchiafava, Pl, Lapi, D, Forini, F, and Iervasi, G.

Subjects
Male, medicine.medical_specialty, Physiology, Antimetabolites, 6-propyl-2-thiouracil, microcirculation, Hamster, Contrast Media, NG-nitro-L-arginine methyl ester, Vasodilation, Iopanoic Acid, arteriole, Nitroarginine, Iopanoic acid, Microcirculation, nitric oxide, In vivo, Cheek pouch, Arteriole, Physiology (medical), Internal medicine, medicine.artery, Cricetinae, medicine, Animals, Enzyme Inhibitors, vasodilation, thyroid hormones, Mouth, Triiodothyronine, Mesocricetus, business.industry, NG-nitro-L-arginine, Arterioles, Thyroxine, Endocrinology, NG-Nitroarginine Methyl Ester, Propylthiouracil, Regional Blood Flow, Nitric Oxide Synthase, Cardiology and Cardiovascular Medicine, business, medicine.drug
Abstract

The aim of the present study was to assess the effects of topically applied triiodothyronine (T3) and thyroxine (T4) on the arterioles of hamster cheek pouch microcirculation in vivo. Microvessels were visualized using a fluorescent microscopy technique. Topical application of T3(3.08, 30.8, 61.5, 307, 615, and 6,150 nM/l) consistently induced dose-dependent dilation of arterioles within 2.0 ± 0.5 min of administration. The application of T4(150, 257, 514, and 5,140 nM/l) caused different dose-dependent effects: dilation at the three lower doses within 16 ± 2 min and rhythmic diameter changes at the highest dose. Aging of hamsters did not alter the arteriolar responses to T3and T4. T3-induced dilation was countered by the inhibition of nitric oxide synthase with NG-nitro-l-arginine-methyl ester or NG-nitro-l-arginine. Iopanoic acid (IPA), which inhibits types I and II 5′-deiodinase, abolished the dilation elicited by 514 nM T4but did not affect T3-dependent dilation. 6-Propyl-2-thiouracil (PTU), which inhibits type I 5′-deiodinase only, did not affect the dilation induced by T4. IPA and PTU did not impair arteriolar dilation induced by acetylcholine or sodium nitroprusside. These results indicate that T3induces arteriolar dilation, likely through nitric oxide release. The local conversion of T4to T3appears to be crucial for the dilation induced by T4.

Published
2005

36. Time course of 21-hydroxylase antibodies and long-term remission of subclinical autoimmune adrenalitis after corticosteroid therapy: case report

Author

Gianfranco Abbate, Stefano Laureti, Silvia Perrino, Francesca Forini, Elio Bizzarro, Antonio Bellastella, Annamaria De Bellis, Antonio Bizzarro, Concetta Coronella, Alberto Falorni, DE BELLIS, Annamaria, Falorni, A, Laureti, S, Perrino, S, Coronella, C, Forini, F, Bizzarro, E, Bizzarro, Antonio, Abbate, Gf, Bellastella, A., and Abbate, G

Subjects
Adrenal Cortex Diseases, Adult, medicine.medical_specialty, Time Factors, Hydrocortisone, medicine.drug_class, Endocrinology, Diabetes and Metabolism, Graves' disease, Clinical Biochemistry, autoanticorpi, Biochemistry, Morbo di Addison, prevenzione, 21-idrossilasi, immunoterapia, Antibodies, Autoimmune Diseases, Endocrinology, Adrenocorticotropic Hormone, Adrenal Cortex Hormones, Immunopathology, Internal medicine, medicine, Adrenal insufficiency, Humans, Aldosterone, Subclinical infection, Autoimmune disease, biology, business.industry, Biochemistry (medical), Autoantibody, 21-Hydroxylase, food and beverages, medicine.disease, eye diseases, Graves Disease, stomatognathic diseases, biology.protein, Corticosteroid, Prednisone, Female, Steroid 21-Hydroxylase, business, Biomarkers, Follow-Up Studies
Abstract

Subclinical Addison's disease is characterized by the presence of adrenal autoantibodies (ACA) and steroid 21-hydroxylase autoantibodies (21OHAb) with or without adrenal function failure. In our previous longitudinal study some patients with high titers of ACA and at stage 2 of subclinical adrenocortical failure showed disappearance of ACA with recovery of normal adrenocortical function after corticosteroid treatment for Graves' ophthalmopathy. To investigate whether corticosteroid-induced modification of the adrenal autoimmune markers can also involve 21OHAb and to evaluate whether the remission of subclinical adrenocortical failure can persist over a long period of time, we followed-up for 100 months the levels of 21OHAb and ACA as well as the metabolic markers of adrenal function in one patient with Graves' ophthalmopathy and at stage 2 of subclinical adrenocortical failure before and after corticosteroid therapy. A 34-yr-old woman with Graves' disease and active ophthalmopathy who was found to be positive for ACA and to have high PRA, low aldosterone levels, and normal basal ACTH and cortisol levels, but impaired cortisol response to ACTH was studied. The patient was treated with oral corticosteroid therapy for 6 months. After corticosteroid therapy, 21OHAb, initially positive, became negative in concomitance with the disappearance of ACA and the restoration of normal adrenal function. The disappearance of both 21OHAb and ACA and their prolonged absence during the follow-up suggest that corticosteroid treatment can induce long-term remission of subclinical adrenal insufficiency and prevent the onset of the clinical phase of the disease. Our pilot study may pave the way to future trials aimed at preventing the onset of the clinical signs of Addison's disease in ACA/21OHAb-positive patients.

Published
2001

37. Oral supplementation of inositols effectively recovered lithium-induced cardiac dysfunctions in mice.

Author

L'Abbate S, Nicolini G, Forini F, Lepore E, Marchetti S, Unfer V, Forte G, and Kusmic C

Subjects
Animals, Male, Mice, Administration, Oral, Lithium administration & dosage, Lithium pharmacology, Myocytes, Cardiac drug effects, Myocytes, Cardiac pathology, Myocytes, Cardiac metabolism, Arrhythmias, Cardiac chemically induced, Arrhythmias, Cardiac prevention & control, Arrhythmias, Cardiac drug therapy, Heart Diseases chemically induced, Heart Diseases prevention & control, Heart Diseases pathology, Heart Diseases drug therapy, Mice, Inbred C57BL, Dietary Supplements, Inositol pharmacology, Inositol administration & dosage
Abstract

This study investigates the effects of inositol (INO) supplementation on cardiac changes caused by Li in mice. The study involved 4 groups of C57BL6 mice (n=10 each): (i) mice orally administered with Li 2 CO 3 for 8 weeks, then 4 additional weeks without (Li_group) or (ii) with INO supplementation (Li_INOdelayed_group) (total of 12 weeks); (iii) mice given Li 2 CO 3 and INO supplementation concurrently for 12 weeks (Li+INO_group); (iv) one group left untreated (C-group). The INO was administered as a mixture of myo-inositol and d-chiro-inositol (80:1) in drinking water. The mice were characterised for heart morphology, function, electrical activity, arrhythmogenic susceptibility, and multiorgan histopathology (heart, liver and kidney). Cardiomyocyte size, protein expression of key signalling pathways related to hypertrophy, and transcription levels of ion channel subunits and hypertrophy markers were evaluated in the ventricle tissue. The study found that INO supplementation reduced the Li-induced cardiac adverse effects, including systolic impairment and increased susceptibility to arrhythmias. The positive effect on arrhythmias might be attributed to the restored expression levels of the potassium channel subunit Kv 1.5. Additionally, INO improved cardiomyocyte hypertrophy, possibly by inhibiting the Li-induced activation of the ERK1/2 signalling pathway and by restoring the normal expression level of BNP, and alleviated injury in the liver and kidney. The effect was preventive if INO supplementation was taken concurrently with Li and therapeutic if INO was administered after Li-induced cardiac impairments were established. These results provide new insights into the cardioprotective effect of INO and suggest a potential treatment approach for Li-induced cardiac disease., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Claudia Kusmic reports equipment, drugs, or supplies was provided by LoLi Pharma Srl. Elisa Lepore reports a relationship with LoLi Pharma Srl that includes: employment. Giampiero Forte reports a relationship with LoLi Pharma Srl that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Published
2024
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38. Effects of sacubitril-valsartan on remodelling, fibrosis and mitochondria in a murine model of isoproterenol-induced left ventricular dysfunction.

Author

Vergaro G, Del Franco A, Carecci A, Ferrari Chen YF, Aimo A, Forini F, Nicolini G, Kusmic C, Faita F, Castiglione V, De Tata V, Pucci A, Musetti V, Burchielli S, Passino C, and Emdin M

Subjects
Animals, Mice, Male, Mice, Transgenic, Mitochondria, Heart drug effects, Mitochondria, Heart metabolism, Angiotensin Receptor Antagonists pharmacology, Random Allocation, Valsartan, Aminobutyrates pharmacology, Biphenyl Compounds pharmacology, Drug Combinations, Disease Models, Animal, Ventricular Remodeling drug effects, Tetrazoles pharmacology, Fibrosis chemically induced, Ventricular Dysfunction, Left chemically induced, Ventricular Dysfunction, Left physiopathology, Isoproterenol toxicity
Abstract

Background: Sacubitril/valsartan has been demonstrated to promote left ventricular (LV) reverse remodelling and improve outcomes in patients with heart failure (HF) with reduced ejection fraction (EF). Its molecular and tissue effects have not been fully elucidated yet, due to the paucity of preclinical studies, mostly based on ischaemic models. We aimed to evaluate the effects of sacubitril/valsartan on LV remodelling, myocardial fibrosis and mitochondrial biology in a murine model of non-ischaemic LV dysfunction., Methods: Adult transgenic male mice with cardiac-specific hyperaldosteronism (AS mice) received subcutaneous isoproterenol injections to induce LV systolic dysfunction. After 7 days, mice were randomized to a 2-week treatment with saline (ISO-AS n = 15), valsartan (ISO + V n = 12) or sacubitril/valsartan (ISO + S/V n = 12). Echocardiography was performed at baseline, at day 7, and after each of the 2 weeks of treatment. After sacrifice at day 21, histological and immunochemical assays were performed. A control group of AS mice was also obtained (Ctrl-AS n = 8)., Results: Treatment with sacubitril/valsartan, but not with valsartan, induced a significant improvement in LVEF (p = 0.009 vs ISO-AS) and fractional shortening (p = 0.032 vs ISO-AS) after 2- week treatment. In both ISO + V and ISO + S/V groups, a trend toward reduction of the cardiac collagen 1/3 expression ratio was detected. ISO + V and ISO + S/V groups showed a significant recovery of mitochondrial morphology and inner membrane function meant for oxidative phosphorylation., Conclusion: In a murine model of non-ischaemic HF, sacubitril/valsartan proved to have beneficial effects on LV systolic function, and on cardiac energetics, by improving mitochondrial activity., Competing Interests: Declaration of competing interest The authors have nothing to declare., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Published
2024
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39. Editorial: Mitochondrial plasticity and quality control in health and disease.

Author

Forini F, Levantini E, Bramanti E, Santorelli FM, Ali A, Lionetti V, and Rizzo M

Abstract

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Published
2024
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40. Thyroid Hormone Signaling in Retinal Development and Function: Implications for Diabetic Retinopathy and Age-Related Macular Degeneration.

Author

Nicolini G, Casini G, Posarelli C, Amato R, Lulli M, Balzan S, and Forini F

Subjects
Humans, Animals, Diabetic Retinopathy metabolism, Diabetic Retinopathy etiology, Diabetic Retinopathy pathology, Macular Degeneration metabolism, Macular Degeneration pathology, Thyroid Hormones metabolism, Retina metabolism, Retina pathology, Signal Transduction
Abstract

Thyroid Hormones (THs) play a central role in the development, cell growth, differentiation, and metabolic homeostasis of neurosensory systems, including the retina. The coordinated activity of various components of TH signaling, such as TH receptors (THRs) and the TH processing enzymes deiodinases 2 and 3 (DIO2, DIO3), is required for proper retinal maturation and function of the adult photoreceptors, Müller glial cells, and pigmented epithelial cells. Alterations of TH homeostasis, as observed both in frank or subclinical thyroid disorders, have been associated with sight-threatening diseases leading to irreversible vision loss i.e., diabetic retinopathy (DR), and age-related macular degeneration (AMD). Although observational studies do not allow causal inference, emerging data from preclinical models suggest a possible correlation between TH signaling imbalance and the development of retina disease. In this review, we analyze the most important features of TH signaling relevant to retinal development and function and its possible implication in DR and AMD etiology. A better understanding of TH pathways in these pathological settings might help identify novel targets and therapeutic strategies for the prevention and management of retinal disease.

Published
2024
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42. Targeting the Translocator Protein (18 kDa) in Cardiac Diseases: State of the Art and Future Opportunities.

Author

Baglini E, Poggetti V, Cavallini C, Petroni D, Forini F, Nicolini G, Barresi E, Salerno S, Costa B, Iozzo P, Neglia D, Menichetti L, Taliani S, and Da Settimo F

Subjects
Humans, Mitochondrial Membranes metabolism, Ligands, Receptors, GABA metabolism, Heart Diseases drug therapy, Heart Diseases metabolism
Abstract

Mitochondria dysfunctions are typical hallmarks of cardiac disorders (CDs). The multiple tasks of this energy-producing organelle are well documented, but its pathophysiologic involvement in several manifestations of heart diseases, such as altered electromechanical coupling, excitability, and arrhythmias, is still under investigation. The human 18 kDa translocator protein (TSPO) is a protein located on the outer mitochondrial membrane whose expression is altered in different pathological conditions, including CDs, making it an attractive therapeutic and diagnostic target. Currently, only a few TSPO ligands are employed in CDs and cardiac imaging. In this Perspective, we report an overview of the emerging role of TSPO at the heart level, focusing on the recent literature concerning the development of TSPO ligands used for fighting and imaging heart-related disease conditions. Accordingly, targeting TSPO might represent a successful strategy to achieve novel therapeutic and diagnostic strategies to unravel the fundamental mechanisms and to provide solutions to still unanswered questions in CDs.

Published
2024
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43. Local modulation of thyroid hormone signaling in the retina affects the development of diabetic retinopathy.

Author

Forini F, Nicolini G, Amato R, Balzan S, Saba A, Bertolini A, Andreucci E, Marracci S, Melecchi A, Terlizzi D, Zucchi R, Iervasi G, Lulli M, and Casini G

Subjects
Mice, Animals, Retina metabolism, Thyroid Hormones metabolism, Gene Expression, Diabetic Retinopathy genetics, Diabetic Retinopathy metabolism, MicroRNAs genetics, MicroRNAs metabolism, Diabetes Mellitus metabolism
Abstract

Thyroid hormone (TH) dyshomeostasis is associated with poor prognosis in acute and prolonged illness, but its role in diabetic retinopathy (DR) has never been investigated. Here, we characterized the TH system in the retinas of db/db mice and highlighted regulatory processes in MIO-M1 cells. In the db/db retinas, typical functional traits and molecular signatures of DR were paralleled by a tissue-restricted reduction of TH levels. A local condition of low T3 (LT3S) was also demonstrated, which was likely to be induced by deiodinase 3 (DIO3) upregulation, and by decreased expression of DIO2 and of TH receptors. Concurrently, T3-responsive genes, including mitochondrial markers and microRNAs (miR-133-3p, 338-3p and 29c-3p), were downregulated. In MIO-M1 cells, a feedback regulatory circuit was evidenced whereby miR-133-3p triggered the post-transcriptional repression of DIO3 in a T3-dependent manner, while high glucose (HG) led to DIO3 upregulation through a nuclear factor erythroid 2-related factor 2-hypoxia-inducible factor-1 pathway. Finally, an in vitro simulated condition of early LT3S and hyperglycemia correlated with reduced markers of both mitochondrial function and stress response, which was reverted by T3 replacement. Together, the data suggest that, in the early phases of DR, a DIO3-driven LT3S may be protective against retinal stress, while, in the chronic phase, it not only fails to limit HG-induced damage, but also increases cell vulnerability likely due to persistent mitochondrial dysfunction., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Published
2024
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44. Dietary Patterns, Gut Microbiota Remodeling, and Cardiometabolic Disease.

Author

Guiducci L, Nicolini G, and Forini F

Abstract

The cardiovascular and metabolic disorders, collectively known as cardiometabolic disease (CMD), are high morbidity and mortality pathologies associated with lower quality of life and increasing health-care costs. The influence of the gut microbiota (GM) in dictating the interpersonal variability in CMD susceptibility, progression and treatment response is beginning to be deciphered, as is the mutualistic relation established between the GM and diet. In particular, dietary factors emerge as pivotal determinants shaping the architecture and function of resident microorganisms in the human gut. In turn, intestinal microbes influence the absorption, metabolism, and storage of ingested nutrients, with potentially profound effects on host physiology. Herein, we present an updated overview on major effects of dietary components on the GM, highlighting the beneficial and detrimental consequences of diet-microbiota crosstalk in the setting of CMD. We also discuss the promises and challenges of integrating microbiome data in dietary planning aimed at restraining CMD onset and progression with a more personalized nutritional approach.

Published
2023
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45. Activated fibroblasts in cardiac and cancer fibrosis: An overview of analogies and new potential therapeutic options.

Author

Nicolini G, Balzan S, and Forini F

Subjects
Humans, Mechanotransduction, Cellular, Fibroblasts metabolism, Myofibroblasts metabolism, Fibrosis, Myocardium metabolism, Epigenesis, Genetic, Neoplasms metabolism
Abstract

Heart disease and cancer are two major causes of morbidity and mortality in the industrialized countries, and their increasingly recognized connections are shifting the focus from single disease studies to an interdisciplinary approach. Fibroblast-mediated intercellular crosstalk is critically involved in the evolution of both pathologies. In healthy myocardium and in non-cancerous conditions, resident fibroblasts are the main cell source for synthesis of the extracellular matrix (ECM) and important sentinels of tissue integrity. In the setting of myocardial disease or cancer, quiescent fibroblasts activate, respectively, into myofibroblasts (myoFbs) and cancer-associated fibroblasts (CAFs), characterized by increased production of contractile proteins, and by a highly proliferative and secretory phenotype. Although the initial activation of myoFbs/CAFs is an adaptive process to repair the damaged tissue, massive deposition of ECM proteins leads to maladaptive cardiac or cancer fibrosis, a recognized marker of adverse outcome. A better understanding of the key mechanisms orchestrating fibroblast hyperactivity may help developing innovative therapeutic options to restrain myocardial or tumor stiffness and improve patient prognosis. Albeit still unappreciated, the dynamic transition of myocardial and tumor fibroblasts into myoFbs and CAFs shares several common triggers and signaling pathways relevant to TGF-β dependent cascade, metabolic reprogramming, mechanotransduction, secretory properties, and epigenetic regulation, which might lay the foundation for future antifibrotic intervention. Therefore, the aim of this review is to highlight emerging analogies in the molecular signature underlying myoFbs and CAFs activation with the purpose of identifying novel prognostic/diagnostic biomarkers, and to elucidate the potential of drug repositioning strategies to mitigate cardiac/cancer fibrosis., Competing Interests: Declaration of competing interest No conflict interest, (Copyright © 2023 Elsevier Inc. All rights reserved.)

Published
2023
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46. Ultrastructural and Molecular Investigation on Peripheral Leukocytes in Alzheimer's Disease Patients.

Author

Giannelli R, Canale P, Del Carratore R, Falleni A, Bernardeschi M, Forini F, Biagi E, Curzio O, and Bongioanni P

Subjects
Humans, Brain pathology, Microglia pathology, Leukocytes pathology, Biomarkers, Disease Progression, Alzheimer Disease pathology, Cognitive Dysfunction pathology
Abstract

Thriving literature underlines white blood cell involvement in the inflammatory processes of Alzheimer's Disease (AD). Among leukocytes, lymphocytes have been considered sentinels of neuroinflammation for years, but recent findings highlighted the pivotal role of neutrophils. Since neutrophils that infiltrate the brain through the brain vascular vessels may affect the immune function of microglia in the brain, a close investigation of the interaction between these cells is important in understanding neuroinflammatory phenomena and the immunological aftermaths that follow. This study aimed to observe how peripheral leukocyte features change at different stages of AD to identify potential molecular markers when the first features of pathological neurodegeneration arise. For this purpose, the examined patients were divided into Mild Cognitive Impairment (MCI) and severely impaired patients (DAT) based on their Cognitive Dementia Rating (CDR). The evaluation of the neutrophil-to-lymphocytes ratio and the morphology and function of leukocytes showed a close relationship between the ultrastructural and the molecular features in AD progression and suggested putative markers for the early stages of the disease., Competing Interests: The authors declare no conflict of interest.

Published
2023
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48. Gut Microbiota and Sex Hormones: Crosstalking Players in Cardiometabolic and Cardiovascular Disease.

Author

Maffei S, Forini F, Canale P, Nicolini G, and Guiducci L

Subjects
Dysbiosis, Gonadal Steroid Hormones metabolism, Humans, Cardiovascular Diseases etiology, Gastrointestinal Microbiome physiology, Microbiota
Abstract

The available evidence indicates a close connection between gut microbiota (GM) disturbance and increased risk of cardiometabolic (CM) disorders and cardiovascular (CV) disease. One major objective of this narrative review is to discuss the key contribution of dietary regimen in determining the GM biodiversity and the implications of GM dysbiosis for the overall health of the CV system. In particular, emerging molecular pathways are presented, linking microbiota-derived signals to the local activation of the immune system as the driver of a systemic proinflammatory state and permissive condition for the onset and progression of CM and CV disease. We further outline how the cross-talk between sex hormones and GM impacts disease susceptibility, thereby offering a mechanistic insight into sexual dimorphism observed in CVD. A better understanding of these relationships could help unravel novel disease targets and pave the way to the development of innovative, low-risk therapeutic strategies based on diet interventions, GM manipulation, and sex hormone analogues.

Published
2022
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49. Role of miR-133/Dio3 Axis in the T3-Dependent Modulation of Cardiac mitoK-ATP Expression.

Author

Canale P, Nicolini G, Pitto L, Kusmic C, Rizzo M, Balzan S, Iervasi G, and Forini F

Subjects
Adenosine Triphosphate metabolism, Animals, Hydrogen Peroxide metabolism, Potassium Channels metabolism, Rats, Triiodothyronine metabolism, Triiodothyronine pharmacology, MicroRNAs genetics, MicroRNAs metabolism, Mitochondria, Heart metabolism
Abstract

The opening of the ATP-sensitive mitochondrial potassium channel (mitok-ATP) is a common goal of cardioprotective strategies in the setting of acute and chronic myocardial disease. The biologically active thyroid hormone (TH), 3-5-3-triiodothyronine (T3), has been indicated as a potential activator of mitoK-ATP but the underlying mechanisms are still elusive. Here we describe a novel role of T3 in the transcriptional regulation of mitoK and mitoSur, the recently identified molecular constituents of the channel. To mimic human ischemic heart damage, we used a rat model of a low T3 state as the outcome of a myocardial ischemia/reperfusion event, and neonatal rat cardiomyocytes (NRCM) challenged with hypoxia or H 2 O 2 . Either in the in vivo or in vitro models, T3 administration to recover the physiological concentrations was able to restore the expression level of both the channel subunits, which were found to be downregulated under the stress conditions. Furthermore, the T3-mediated transcriptional activation of mitoK-ATP in the myocardium and NRCM was associated with the repression of the TH-inactivating enzyme, deiodinase 3 (Dio3), and an up-regulation of the T3-responsive miR-133a-3p. Mechanistically, the loss and gain of function experiments and reporter gene assays performed in NRCM, have revealed a new regulatory axis whereby the silencing of Dio3 under the control of miR-133a-3p drives the T3-dependent modulation of cardiac mitoK and mitoSur transcription.

Published
2022
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50. Mitochondria-Targeted Drug Delivery in Cardiovascular Disease: A Long Road to Nano-Cardio Medicine.

Author

Forini F, Canale P, Nicolini G, and Iervasi G

Abstract

Cardiovascular disease (CVD) represents a major threat for human health. The available preventive and treatment interventions are insufficient to revert the underlying pathological processes, which underscores the urgency of alternative approaches. Mitochondria dysfunction plays a key role in the etiopathogenesis of CVD and is regarded as an intriguing target for the development of innovative therapies. Oxidative stress, mitochondrial permeability transition pore opening, and excessive fission are major noxious pathways amenable to drug therapy. Thanks to the advancements of nanotechnology research, several mitochondria-targeted drug delivery systems (DDS) have been optimized with improved pharmacokinetic and biocompatibility, and lower toxicity and antigenicity for application in the cardiovascular field. This review summarizes the recent progress and remaining obstacles in targeting mitochondria as a novel therapeutic option for CVD. The advantages of nanoparticle delivery over un-targeted strategies are also discussed.

Published
2020
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