Hypertension Induces Pro-arrhythmic Cardiac Connexome Disorders: Protective Effects of Treatment

Figures

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  Figure 2. Connexomes are identified on the lateral sides of the hypertrophied guinea pig cardiomyocytes. Their AJ, D, and GJ components are destroyed by progressive extracellular collagen deposition [21]. Scale bar represents 1 micrometer.

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  Figure 1. Intercalated discs comprise three distinct junctional complexes, the “connexome”: adherens junction (AJ), desmosome (D), and gap junction (GJ). These work together to mediate cardiomyocyte mechanical and electrical coupling. There are also various interacting proteins that can modulate connexome function [10,12,13,14,15,16,17,18]. Disorders of this complex structure appear to be pro-arrhythmic and promote mechanical heart dysfunction.Electron microscopic images adapted from [11].

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  Figure 3. Tentative connexome implications in pro-arrhythmic disorders induced by HTN and PAH.

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  Figure 4. AF and VF aggravate connexome impairment. This includes AJ, D, and GJ due to Ca2 -overload, ischemia, and other factors. The subcellular rat heart alterations shown in the (A–C) images indicate desynchronized contraction of neighboring cardiomyocytes, and image (D) shows varying degrees of injury attributed to connexome impairment. Scale bar represents 0.1 micrometer. Adapted from [19].

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  Figure 5. Electron microscope images demonstrate connexome occurrence in SHR hearts. There is formation of the connexome lateral junctions in hypertrophied cardiomyocytes (A–C), and their presence on the lateral sides with those at the intercalated disc (D). A long lateral GJ is obvious in the SHR heart (E), and its degradation and the formation of annular profile (aGJ) occur with HTN progression (F). Scale bar represents 1 micrometer. Adapted from [54,73].

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  Figure 6. Electron microscope images illustrate connexome impairment in SHR hearts. Varying degrees of AJ dehiscence are apparent in images (A–C), and these are accompanied by GJs loss. The connexome impairment also results in asynchronized contractions of neighbouring cardiomyocytes (A,D). Long-lasting HTN related structural remodeling includes severely injured cardiomyocytes, with the destroyed connexome at the intercalated disc (arrowhead in (E)) and on the cardiomyocytes lateral side (F). This is accompanied with progressive fibrosis. Scale bar represents 1 micrometer. Adapted from [3].

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  Figure 7. Proposed factors and mechanisms that may be involved in pro-arrhythmic “connexome” dysfunction in chronic arterial hypertension.