Localization and quantitation of cardiac annexins II, V, and VI in hypertensive guinea pigs

Abstract

Annexins are characterized by Ca2+-dependent binding to phospholipids. Annexin II mainly participates in cell-cell adhesion and signal transduction, whereas annexins V and VI also seem to regulate intracellular calcium cycling. Their abundance and localization were determined in left ventricle (LV) and right ventricle (RV) from hypertensive guinea pigs, during the transition from compensatory hypertrophy to heart failure. Immunoblot analysis of annexins II, V, and VI revealed an increased accumulation (2.6-, 1.45-, and 2.3-fold, respectively) in LV from hypertensive guinea pigs and no modification in RV. Immunofluorescent labeling of annexins II, V, and VI; of Na+-K+-ATPase; and of sarcomeric α-actinin showed that in control LV and RV, 1) annexin II is present in nonmuscle cells; 2) annexins V and VI are mainly observed in the sarcolemma and intercalated disks of myocytes; 3) annexins II, V, and VI strongly label endothelial cells and adventitia of coronary arteries; and 4) annexin VI is present in the media. At the onset of heart failure, the most striking changes are the increased protein accumulation in LV and the very strong labeling of annexins II, V, and VI in interstitial tissue, suggesting a role in fibrosis development and cardiac remodeling.

Expression and Localization of the Annexins II, V, and VI in Myocardium from Patients with End-Stage Heart Failure

“…Myocardial annexins have been mostly studied in animal species in which annexins II, V, and VI are particularly abundant. The annexin II has been found in rat (Jans et al, 1995), bovine (Zeng et al, 1993), and guinea pig (Trouvé et al, 1999) myocardium. In different tissues, annexin II has been reported to bind collagen, to promote contacts between vesicles, and to be involved in regulation of cell-extracellular matrix interactions (Waisman, 1995).…”

“…Another important feature of annexin II is its inhibitory activity on G proteinregulated ip 3 production, suggesting a role in the development of hypertension (Schelling et al, 1996). Annexins V and VI are the major annexins in porcine (Pula et al, 1990), bovine (Iida et al, 1992;Wang et al, 1993;Zeng et al, 1993), rat (Doubell et al, 1993;Jans et al, 1995;Wang et al, 1995), and guinea pig (Trouvé et al, 1999) myocardium. Annexin V is able to form voltage-gated Ca 2ϩ channels (Pollard et al, 1992) and to modulate activity of protein kinase C and phospholipase A 2 Mira et al, 1998;Van Bilsen et al, 1992).…”

“…Annexin V is able to form voltage-gated Ca 2ϩ channels (Pollard et al, 1992) and to modulate activity of protein kinase C and phospholipase A 2 Mira et al, 1998;Van Bilsen et al, 1992). In myocardium, the localization of annexin V is not clearly established: the presence of annexin V was first reported in endothelium and fibroblasts (Van Bilsen et al, 1992), then in myocytes in which it has been detected either in cytosol (Jans et al, 1995), in membranes (Luckcuck et al, 1997;Trouvé et al, 1999), or associated with Z-lines (Trouvé et al, 1999;Wang et al, 1995). Annexin VI has been localized in rat, bovine, and guinea pig hearts mainly in sarcolemma and intercalated discs of cardiomyocytes (Doubell et al, 1993;Iida et al, 1992;Luckcuck et al, 1997;Trouvé et al, 1999).…”

“…Overexpression of annexin VI in the heart of transgenic mice was shown to result in dilated cardiomyopathy (Gunteski-Hamblin et al, 1996) with impaired contractility and intracellular Ca 2ϩ turnover (Song et al, 1995). Increases in the levels of annexins II, V, and VI were found in hypertensive guinea pigs at the onset of heart failure (Trouvé et al, 1999) and increases of annexins II and V, together with a decrease of annexin VI in failing human heart (Song et al, 1998). However, potential roles for annexins in heart failure cannot be considered without establishing their precise distribution in human heart and during heart failure.…”

Effect of water-soluble fraction of cigarette smoke on human aortic endothelial cells – a proteomic approach

“…They may also be relevant to fibrosis and remodeling of cardiovascular system (Benevolensky et al, 2000;Trouve et al, 1999). Although on the surface this may appear to be contradictory to the global pro-thrombotic effects by the cigarettes, one must bear in mind that annexin expression in endothelial cells only represents one small aspect of the entire thrombotic cascades.…”