Sarcoplasmic reticulum Ca2+ ATPase gene expression to the rescue of myocardial contractility in hypothyroid associated heart failure.

See article by Bluhm et al. [18] (pages 382 –388) in this hypertrophy has led to the proposal that hypertrophy itself issue. may recapitulate ontogeny [13–15]. Therefore, the heart failure process that occurs in the context of myocardial Recent advances in animal genetics and transgenic hypertrophy or complex metabolic disorders that impact technology have blossomed into one of the dominant the cardiovascular system is closely entangled with the strategies to explore the consequences of gene defects in impairment of the myocyte program of growth and difdifferent organ systems in the in vivo context. Such a ferentiation. These considerations pose the problem of perspective has been progressively applied to the caridentifying endogenous molecules that can restore the diovascular system to dissect complex in vivo physiologic myocardial contractility in the course of diseases bearing a and pathologic states. The encouraging results achieved so complex genetic background, including different types of far in the field of heart hypertrophy and failure with the aid acquired or genetically determined myocardial hyperof engineered mouse models have even suggested considtrophy, hereditary cardiomyopathies, and cardiomyopathic eration for the cardiovascular system as a paradigm for processes associated with diabetes or hypothyroidism. The 21 other complex apparata, including the pulmonary, renal calcium pump, or Ca -ATPase of the sarcoplasmic and neural systems [1]. reticulum (SERCA2a) is now recognized as a major It is now becoming increasingly evident that the regulator of cardiac contractile function. This pump drives 21 myocardial cell, besides being a target for a number of the Ca uptake into the sarcoplasmic reticulum, therefore hormones and growth factors [2,3] also behaves as a accounting for the speed of cardiac relaxation. Consonant source for peptides that may play a crucial role in signal with a crucial role of SERCA2a in contractile regulation is transduction processes in the heart [4–7]. Hence, the the observation that a decrease in SERCA2a gene expresmyocardium adapts to hormonal, genetic and mechanical sion and activity can be observed in a wide variety of stimuli by triggering a number of paracrine, autocrine and pathological conditions associated with cardiac hyperintracrine responses that represent the plight that is impacttrophy and/or failure [16,17]. ing the homeostasis of the myocardial cells throughout In this issue of Cardiovascular Research, Bluhm et al. specific pathologic processes [8–11]. The complexity of [18] examined the possibility that transgenic gene expresthe overall picture is given by the finding that heart sion of SERCA2a in mice may compensate for the mechanical dysfunctions and failure are often the funcabnormalities in cardiac performance associated with tional end-point of processes involving an impairment of pharmacologically-induced hypothyroidism. The authors the architectural plan of the myocardial cell [1,12]. In this assessed SERCA2a gene and protein expression in hearts regard, heart development is one of the first morphogenetic from euthyroid and hypothyroid mice of wild-type or events occurring in the embryo and is a complex phenomSERCA2a transgene status. The study revealed a decrease enon involving cell proliferation and differentiation, as in SERCA2a mRNA and protein expression in hypothyroid well as tissue organization. The observation that a rewild-type animals, as compared with euthyroid wild-type capitulation of the fetal program occurs during myocardial mice. Such a decrease was associated with a prolongation in the time course of both the contraction and relaxation in