title: Structural remodelling of the sinoatrial node in obese old rats.
abstract: During ageing, the function of sinoatrial node (SAN), the pacemaker of the heart, declines, and the incidence of sick sinus syndrome increases markedly. The aim of the study was to investigate structural and functional remodelling of the SAN during ageing. Rats, 3 and 24 months old (equivalent to young adult and approximately 69-year-old humans), were studied. Extracellular potential recording from right atrial preparations showed that (as expected) the intrinsic heart rate was slower in the old animals. It also showed a shift of the leading pacemaker site towards the inferior vena cava in the old animals. Consistent with this, intracellular potential recording showed that slow pacemaker action potentials were more widespread and extended further towards the inferior vena cava in old animals. Immunohistochemistry demonstrated that SAN tissue expressing HCN4, but lacking the expression of Na(v)1.5 (lack of Na(v)1.5 explains why pacemaker action potential is slow), was also more widespread and extended further towards the inferior vena cava in the old animals. Immunolabelling of caveolin3 (expressed in cell membrane of cardiac myocytes) demonstrated that there was a hypertrophy of the SAN cells in the old animals. Histology, quantitative PCR, and immunohistochemistry revealed evidence of a substantial age-dependent remodelling of the extracellular matrix (e.g. approximately 79% downregulation of genes responsible for collagens 1 and 3 and approximately 52% downregulation of gene responsible for elastin). It is concluded that the age- (and/or obesity-) dependent decline in SAN function is associated with a structural remodelling of the SAN: an enlargement of the SAN, a hypertrophy of the SAN cells, and a remodelling of the extracellular matrix.
authors.affiliation: Cardiovascular Medicine, School of Medicine, University of Manchester, Core Technology Facility, 46 Grafton Street, Manchester M13 9NT, UK.
authors.forename: J
authors.initials: J
authors.lastname: Yanni
authors.forename: J O
authors.initials: JO
authors.lastname: Tellez
authors.forename: P V
authors.initials: PV
authors.lastname: Sutyagin
authors.forename: M R
authors.initials: MR
authors.lastname: Boyett
authors.forename: H
authors.initials: H
authors.lastname: Dobrzynski
mesh_terms: D000375:Aging; D000818:Animals; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology; D062554:NAV1.5 Voltage-Gated Sodium Channel; D009765:Obesity / Q000503:physiopathology*; D015221:Potassium Channels / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012849:Sinoatrial Node / Q000473:pathology*; D015222:Sodium Channels / Q000378:metabolism; D013997:Time Factors; D014682:Vena Cava, Inferior / Q000473:pathology
chemical_list: C513836:HCN4 protein, rat; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; D015221:Potassium Channels; C568320:SCN5A protein, human; C466180:Scn4a protein, rat; C568322:Scn5a protein, rat; D015222:Sodium Channels