FIGURE 3.

Alterations in cardiomyocyte t-tubule structure and Ca²⁺ release in different HF entities. (A) Left panels: 3D reconstructions and 2D zoom-ins of t-tubules imaged in human cardiac biopsies (wheat germ agglutinin staining). Healthy individuals are compared with HFpEF patients, with and without diabetes mellitus, and HFrEF patients. As illustrated in the schematics (right panels), t-tubule density is unchanged in diabetic HFpEF, increased in non-diabetic HFpEF, and decreased in HFrEF. In all HF entities, t-tubules dilate. However, whereas t-tubule remodeling is accompanied by increased NCX and SERCA function in non-diabetic HFpEF, Ca²⁺ removal by these proteins is decreased in diabetic HFpEF and HFrEF. (B) T-tubule disruption promotes dyssynchronous and slowed Ca²⁺ release in rats with HFrEF but not HFpEF, while slowed Ca²⁺ removal promotes diastolic dysfunction in diabetic HFpEF and HFrEF. For each disease state, representative Ca²⁺ transients (right panels) are presented with comparison to a control cardiomyocyte (green) for the individual rat models. Micrographs and Ca²⁺ transients are reproduced from Frisk et al. (2021) with permission.