ORCID Profile
0000-0003-0481-6843
Current Organisations
IRCCS Humanitas Research Hospital
,
Humanitas University
,
University of Leicester
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Publisher: Oxford University Press (OUP)
Date: 04-2008
Publisher: Elsevier BV
Date: 10-2014
DOI: 10.1016/J.PHARMTHERA.2014.05.005
Abstract: The morbidity and mortality from ischemic heart disease (IHD) remain significant worldwide. The treatment for acute myocardial infarction has improved over the past decades, including early reperfusion of occluded coronary arteries. Although it is essential to re-open the artery as soon as possible, paradoxically this leads to additional myocardial injury, called acute ischemia-reperfusion injury (IRI), for which currently no effective therapy is available. Therefore, novel therapeutic strategies are required to protect the heart from acute IRI in order to reduce myocardial infarction size, preserve cardiac function and improve clinical outcomes in patients with IHD. In this review article, we will first outline the pathophysiology of acute IRI and review promising therapeutic strategies for cardioprotection. These include novel aspects of mitochondrial function, epigenetics, circadian clocks, the immune system, microvesicles, growth factors, stem cell therapy and gene therapy. We discuss the therapeutic potential of these novel cardioprotective strategies in terms of pharmacological targeting and clinical application.
Publisher: Elsevier BV
Date: 09-2007
Publisher: Public Library of Science (PLoS)
Date: 26-07-2013
Publisher: Informa UK Limited
Date: 2008
DOI: 10.1080/08958370701883821
Abstract: Cigarette smoke contains hundreds of potentially toxic compounds and is an important risk factor for cardiovascular disease. However, the key components responsible for endothelial and myocardial dysfunction have not been fully identified. The objective of the present study was to determine the cardiovascular effects of long-term inhalation of carbon monoxide (CO) administrated to give concentrations in the blood similar to those observed in heavy smokers. Female rats were exposed to either CO or air (control group) (n = 12). The CO group was exposed to 200 ppm CO (100 h/wk) for 18 mo. Rats exposed to CO had 24% lower maximal oxygen uptake, longer (145 vs. 123 microm) and wider (47 vs. 25 microm) cardiomyocytes, reduced cardiomyocyte fractional shortening (12 vs. 7%), and 26% longer time to 50% re-lengthening than controls. In addition, cardiomyocytes from CO-exposed rats had 48% lower intracellular calcium (Ca2 +) litude, 22% longer time to Ca2 + decay, 34% lower capacity of sarcoplasmic reticulum Ca2 +-ATPase (SERCA2a), and 37% less t-tubule area compared to controls. Phosphorylation levels of phospholamban at Ser16 and Thr17 were significantly reduced in the CO group, whereas total concentration of phospholamban and SERCA2a were unchanged. Cardiac atrial natriuretic peptide, vascular endothelial growth factor, cyclic guanosine monophosphate, calcineurin, calmodulin, pERK, and pS6 increased, whereas pAkt and pCaMKII delta remained unchanged by CO. Endothelial function and systemic blood pressure were not affected by CO exposure. Long-term CO exposure reduces aerobe capacity and contractile function and leads to pathological hypertrophy. Impaired Ca2 + handling and increased growth factor signaling seem to be responsible for these pathological changes.
Publisher: Oxford University Press (OUP)
Date: 29-04-2017
DOI: 10.1093/CVR/CVX070
Publisher: Wiley
Date: 25-02-2014
DOI: 10.1111/APHA.12238
Publisher: Public Library of Science (PLoS)
Date: 28-02-2013
Publisher: American Physiological Society
Date: 09-2010
DOI: 10.1152/JAPPLPHYSIOL.01257.2009
Abstract: Diving and decompression performed under immersed conditions have been shown to reduce cardiac function. The mechanisms for these changes are not known. The effect of immersion before a simulated hyperbaric e on cardiomyocyte function was studied. Twenty-three rats were assigned to four groups: control, 1 h thermoneutral immersion, dry e, and 1 h thermoneutral immersion before a e (preimmersion e). Rats exposed to a e were compressed to 700 kPa, maintained for 45 min breathing air, and decompressed linearly to the surface at a rate of 50 kPa/min. Post e, the animals were anesthetized and the right ventricle insonated for bubble detection using ultrasound. Isolation of cardiomyocytes from the left ventricle was performed and studied using an inverted fluorescence microscope with video-based sarcomere spacing. Compared with a dry e, preimmersion e significantly increased bubble production and decreased the survival time (bubble grade 1 vs. 5, and survival time 60 vs. 17 min, respectively). Preimmersion e lead to 18% decreased cardiomyocyte shortening, 20% slower diastolic relengthening, and 22% higher calcium litudes compared with controls. The protein levels of the sarco-endoplasmic reticulum calcium ATPase (SERCA2a), Na + /Ca 2+ exchanger (NCX), and phospholamban phosphorylation in the left ventricular tissue were significantly reduced after both dry and preimmersion e compared with control and immersed animals. The data suggest that immersion before a e results in impaired cardiomyocyte and Ca 2+ handling and may be a cellular explanation to reduced cardiac function observed in humans after a e.
Publisher: American Physiological Society
Date: 26-05-2016
Publisher: Elsevier BV
Date: 08-2013
DOI: 10.1016/J.CELL.2013.07.039
Abstract: The epidemic of heart failure has stimulated interest in understanding cardiac regeneration. Evidence has been reported supporting regeneration via transplantation of multiple cell types, as well as replication of postmitotic cardiomyocytes. In addition, the adult myocardium harbors endogenous c-kit(pos) cardiac stem cells (eCSCs), whose relevance for regeneration is controversial. Here, using different rodent models of diffuse myocardial damage causing acute heart failure, we show that eCSCs restore cardiac function by regenerating lost cardiomyocytes. Ablation of the eCSC abolishes regeneration and functional recovery. The regenerative process is completely restored by replacing the ablated eCSCs with the progeny of one eCSC. eCSCs recovered from the host and recloned retain their regenerative potential in vivo and in vitro. After regeneration, selective suicide of these exogenous CSCs and their progeny abolishes regeneration, severely impairing ventricular performance. These data show that c-kit(pos) eCSCs are necessary and sufficient for the regeneration and repair of myocardial damage.
Publisher: Oxford University Press (OUP)
Date: 24-10-2014
DOI: 10.1093/CVR/CVU225
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-09-2009
DOI: 10.1161/CIRCRESAHA.109.199810
Abstract: Rationale: In the present study we explored the mechanisms behind excitation–contraction (EC) coupling defects in cardiomyocytes from mice with type-2 diabetes (db/db). Objective: We determined whether 13 weeks of aerobic interval training could restore cardiomyocyte Ca 2+ cycling and EC coupling. Methods and Results: Reduced contractility in cardiomyocytes isolated from sedentary db/db was associated with increased diastolic sarcoplasmic reticulum (SR)-Ca 2+ leak, reduced synchrony of Ca 2+ release, reduced transverse (T)-tubule density, and lower peak systolic and diastolic Ca 2+ and caffeine-induced Ca 2+ release. Additionally, the rate of SR Ca 2+ ATPase–mediated Ca 2+ uptake during diastole was reduced, whereas a faster recovery from caffeine-induced Ca 2+ release indicated increased Na + /Ca 2+ -exchanger activity. The increased SR-Ca 2+ leak was attributed to increased Ca 2+ -calmodulin–dependent protein kinase (CaMKIIδ) phosphorylation, supported by the normalization of SR-Ca 2+ leak on inhibition of CaMKIIδ (AIP). Exercise training restored contractile function associated with restored SR Ca 2+ release synchronicity, T-tubule density, twitch Ca 2+ litude, SR Ca 2+ ATPase and Na + /Ca 2+ -exchanger activities, and SR-Ca 2+ leak. The latter was associated with reduced phosphorylation of cytosolic CaMKIIδ. Despite normal contractile function and Ca 2+ handling after the training period, phospholamban was hyperphosphorylated at Serine-16. Protein kinase A inhibition (H-89) in cardiomyocytes from the exercised db/db group abolished the differences in SR-Ca 2+ load when compared with the sedentary db/db mice. EC coupling changes were observed without changes in serum insulin or glucose levels, suggesting that the exercise training–induced effects are not via normalization of the diabetic condition. Conclusions: These data demonstrate that aerobic interval training almost completely restored the contractile function of the diabetic cardiomyocyte to levels close to sedentary wild type.
Publisher: Wiley
Date: 16-10-2007
DOI: 10.1002/JCP.21197
Abstract: Cardiomyocyte hypertrophy differs according to the stress exerted on the myocardium. While pressure overload-induced cardiomyocyte hypertrophy is associated with depressed contractile function, physiological hypertrophy after exercise training associates with preserved or increased inotropy. We determined the activation state of myocardial Akt signaling with downstream substrates and fetal gene reactivation in exercise-induced physiological and pressure overload-induced pathological hypertrophies. C57BL/6J mice were either treadmill trained for 6 weeks, 5 days/week, at 85-90% of maximal oxygen uptake (VO(2max)), or underwent transverse aortic constriction (TAC) for 1 or 8 weeks. Total and phosphorylated protein levels were determined with SDS-PAGE, and fetal genes by real-time RT-PCR. In the physiologically hypertrophied heart after exercise training, total Akt protein level was unchanged, but Akt was chronically hyperphosphorylated at serine 473. This was accompanied by activation of the mammalian target of rapamycin (mTOR), measured as phosphorylation of its two substrates: the ribosomal protein S6 kinase-1 (S6K1) and the eukaryotic translation initiation factor-4E binding protein-1 (4E-BP1). Exercise training did not reactivate the fetal gene program (beta-myosin heavy chain, atrial natriuretic factor, skeletal muscle actin). In contrast, pressure overload after TAC reactivated fetal genes already after 1 week, and partially inactivated the Akt/mTOR pathway and downstream substrates after 8 weeks. In conclusion, changes in opposite directions of the myocardial Akt/mTOR signal pathway appears to distinguish between physiological and pathological hypertrophies exercise training associating with activation and pressure overload associating with inactivation of the Akt/mTOR pathway.
Location: United States of America
Location: United States of America
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Gianluigi Condorelli.