Changes in T-Tubules and Sarcoplasmic Reticulum in Ventricular Myocytes in Early Cardiac Hypertrophy in a Pressure Overload Rat Model

Abstract

Background/Aims: Pressure-overload (PO) causes cardiac hypertrophy (CH), and eventually leads to heart failure (HF). HF ventricular myocytes present transverse-tubules (TT) loss or disarrangement and decreased sarcoplasmic reticulum (SR) density, and both contribute to altered Ca²⁺ signaling and heart dysfunction. It has been shown that TT remodeling precedes HF, however, it is unknown whether SR structural and functional remodeling also starts early in CH. Methods: Using confocal microscopy, we assessed TT (with Di-8-ANNEPS) and SR (with SR-trapped Mag-Fluo-4) densities, as well as SR fluorophore diffusion (fluorescence recovery after photobleach; FRAP), cytosolic Ca²⁺ signaling and ex vivo cardiac performance in a PO rat hypertrophy model induced by abdominal aortic constriction (at 6 weeks). Results: Rats developed CH, while cardiac performance, basal and upon β-adrenergic stimulation, remained unaltered. TT density decreased by ∼14%, without spatial disarrangement, while SR density decreased by ∼7%. More important, FRAP was ∼30% slower, but with similar maximum recovery, suggesting decreased SR interconnectivity. Systolic and diastolic Ca²⁺ signaling and SR Ca²⁺ content were unaltered. Conclusion: SR remodeling is an early CH event, similar to TT remodeling, appearing during compensated hypertrophy. Nevertheless, myocytes can withstand those moderate structural changes in SR and TT, preserving normal Ca²⁺ signaling and contractility.

Regional distribution of T-tubule density in left and right atria in dogs

“…Some of these differences may be species related or related to localization in endocardium compared to epicardium. Since T-tubules can change morphology in response to culture conditions, acute stretch, HF and AF 17, 25, 26 , the smaller percentage of cells exhibiting T-tubules in prior studies may be an artifact of tissue fixation and/or cell isolation. Perhaps most importantly, our study shows that 25% of RA myocytes and 12.5% of LA myocytes completely lack any T-tubules whatsoever.…”

Inhibition of Cardiomyocytes Hypertrophy by Resveratrol Is Associated with Amelioration of Endoplasmic Reticulum Stress

“…Chronic impairment of β-AR signaling contributes to alterations in cardiac structure through increased apoptosis, hypertrophy, fibrosis and steadily decreased contractile function [14,15]. ISO, an agonist of the adrenergic receptor, induces compromised and unstable cardiac hemodynamics and aggravates cell death, thereby inducing HF [16,17]. Apoptosis is a critical step in provoking systolic dysfunction and congestive HF [18].…”

Disruption of transverse‐tubular network reduces energy efficiency in cardiac muscle contraction

“…[10][11][12] It is recognized that t-tubular remodelling establishes prior to the onset of heart failure, early in the disease progression, and represents one of the causal events that drives the transition from compensated hypertrophy to heart failure. [14][15][16] The contribution of t-tubular remodelling to heart failure is boosted by evidence from experiments where the t-tubules are artificially, and acutely, disrupted. Such a technique uncouples t-tubules physically and functionally from the surface membrane by osmotic shock using a membrane-permeant agent, formamide.…”