Pandora's Box: mitochondrial defects in ischaemic heart disease and stroke

Andalib, Sasan; Divani, Afshin A.; Michel, Tanja Maria; Høilund‐Carlsen, Poul Flemming; Vafaee, Manouchehr Seyedi; Gjedde, Albert

doi:10.1017/erm.2017.5

Cited by 21 publications

(8 citation statements)

References 200 publications

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“…When considering the cardiac involvement, P1 presented a second-degree atrioventricular block Mobitz type 2 leading to a pacemaker implantation and P2 had a supraventricular tachycardia medically treated. Incidence of cardiac complications is frequent in patients with mitochondriopathy, either in isolation, or as a component of a multisystem disease (7, 11). Cardiac involvement in mitochondriopathies is heterogeneous, ranging from conduction system disease and rhythm disease, to myocardial abnormalities such hypertrophic and dilated or non-compaction cardiomyopathies (12, 13).…”

Section: Discussionmentioning

confidence: 99%

Novel Phenotypes and Cardiac Involvement Associated With DNA2 Genetic Variants

et al. 2019

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Objectives: To report two novel DNA2 gene mutations causing early onset myopathy with cardiac involvement and late onset mitochondriopathy with rhabdomyolysis.Methods: We performed detailed clinical, muscle histopathology and molecular studies including mitochondrial gene NGS analysis in two patients (Patient 1 and 2), a mother and her son, belonging to a Mexican family, and a third sporadic French patient.Results: Patient 1 and 2 presented with an early onset myopathy associated with ptosis, velopharyngeal weakness, and cardiac involvement. Patient 3 presented rhabdomyolysis unmasking a mitochondrial disease characterized by a sensorineural hearing loss, ptosis, and lipomas. Muscle biopsies performed in all patients showed variable mitochondrial alterations. Patient 3 had multiple mtDNA deletion in his muscle. Genetic studies revealed a novel heterozygous frameshift mutation in DNA2 gene (c.2346delT p.Phe782Leufs*3) in P1 and P2, and a novel heterozygous missense mutation in DNA2 gene (c.578T>C p.Leu193Ser) in the P3.Conclusions: To date only few AD cases presenting either missense or truncating DNA2 variants have been reported. None of them presented with a cardiac involvement or rhabdomyolysis. Here we enlarge the genetic and phenotypic spectrum of DNA2-related mitochondrial disorders.

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Section: Discussionmentioning

confidence: 99%

Novel Phenotypes and Cardiac Involvement Associated With DNA2 Genetic Variants

et al. 2019

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“…two third of stroke patients show these risk factors, however, others must have other unknown risk factors (3)(4)(5). Inflammatory (6) and mitochondrial (7) pathways are involved in stroke. the ischemic injury causes disruption of blood brain barrier, inflammation, and oxidative stress.…”

Section: Original Articlesmentioning

confidence: 99%

Pineal gland calcification confirmed by CT scan is associated with ischemic stroke

Moadabi¹,

Rezaei²,

Homaei-Rad³

et al. 2019

Ro J Neurol.

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background. Stroke is the second leading cause of death and the most common debilitating neurological disorder worldwide. The ischemic injury causes inflammation and oxidative stress, and leads to apoptosis, necrosis and activation of autophagal pathways determining final infarct size. Melatonin, a hormone secreted by the pineal gland, is a small molecule that acts as a free radical scavenger, and performs antioxidant activities in several neurodegenerative diseases. Melatonin secretion reduces in aging due to pineal gland calcification and thus the calcification is a representative of reduced melatonin production. In this study, our aim was to evaluate the association of pineal gland calcification and stroke. Material and methods. An analytical cross sectional single center study was conducted. Pineal gland calcification was assessed by CT scan in 179 patients with ischemic stroke and 177 hospital controls. results. The mean age in the control and stroke groups were 58.18 and 61.2 years, respectively. Pineal gland calcification was found in 77.4% of subjects in the control group and 88.8% of the subjects in the stroke group. Pineal gland calcification, alone, was shown to significantly increase the risk of ischemic stroke (P=0.005; OR=2.3; 95% CI=1.2-4.1). Furthermore, after adjustment for diabetes mellitus, hypertension, hyper lipedema, gender, and age, there was still a significant association of pineal gland calcification with ischemic stroke (P=0.04; OR=2.0; 95% CI=1.0-3.9). conclusion. The evidence from the present study suggests that pineal gland calcification is associated with ischemic stroke.

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“…Recently, there has been interest in the epigenetic mechanisms which control the expression of genes in coronary heart disease and mitochondria [19,20]. Quaking (QKI) is a member of the transduction and activation of RNA (STAR) family of RNA-binding proteins (RBPs) involved in various forms of epigenetic processing, such as pre-mRNA splicing and controlling the stability and turnover of microRNA (miRNA) [21,22].…”

Section: Introductionmentioning

confidence: 99%

SOCS-6 promotes mitochondrial fission and cardiomyocyte apoptosis and is negatively regulated by QKI mediated miR-19b

Zhang¹,

Guan²,

Ye³

et al. 2020

Preprint

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Background Ischemia/reperfusion (IR) injury following myocardial infarction can result in debilitating complications and morbidity. Mitochondrial dysfunction and abnormal mitochondrial fission have been implicated in the complications associated with IR injury as cardiomyocytes are abundant in mitochondria. SOCS-6 is known to participate in mitochondrial fragmentation but its exact involvement and the pathways associated are uncertain. Results In the present study, we examine the biological role and regulation of SOCS-6 in mitochondrial dynamics using hypoxia and reoxygenation (H/R) in cardiomyocytes and with a murine model of IR injury. We found that SOCS-6 inhibition by RNA interference attenuated H/R-induced mitochondrial fission and apoptosis in cardiomyocytes. A luciferase assay indicated that SOCS-6 is a direct target of miR-19b. The overexpression of miR-19b decreased mitochondrial fission and apoptosis in vitro . Moreover, the presence of miR-19b reduced the level of SOCS-6 and the injury caused by IR in vivo . There were less apoptotic cells in the myocardium of mice injected with miR-19b. In addition, we found that the RNA-binding protein, QKI, participates in the regulation of miR-19b expression. Conclusions Our results indicate that the inhibition of mitochondrial fission through downregulating SOCS-6 via the QKI/miR-19b/SOCS-6 pathway attenuated the damage sustained by IR. The QKI/miR-19b/SOCS-6 axis plays a vital role in regulation of mitochondrial fission and cardiomyocyte apoptosis and could form the basis of future research in the development of therapies for the management of cardiac diseases.

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Pandora's Box: mitochondrial defects in ischaemic heart disease and stroke

Cited by 21 publications

References 200 publications

Novel Phenotypes and Cardiac Involvement Associated With DNA2 Genetic Variants

Novel Phenotypes and Cardiac Involvement Associated With DNA2 Genetic Variants

Pineal gland calcification confirmed by CT scan is associated with ischemic stroke

SOCS-6 promotes mitochondrial fission and cardiomyocyte apoptosis and is negatively regulated by QKI mediated miR-19b

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