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Role of TGF-beta on cardiac structural and electrical remodeling.

Ramos-Mondragón R, Galindo CA, Avila G - Vasc Health Risk Manag (2008)

Bottom Line: This fact is surprising since electrical remodeling represents an important substrate for cardiac disease.This review discusses the potential role of TGF-beta on cardiac excitation-contraction (EC) coupling, action potentials, and ion channels.We also discuss the effects of TGF-beta on cardiac development and disease from structural and electrophysiological points of view.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Bioquímica, Cinvestav-IPN, México.

ABSTRACT
The type beta transforming growth factors (TGF-betas) are involved in a number of human diseases, including heart failure and myocardial arrhythmias. In fact, during the last 20 years numerous studies have demonstrated that TGF-beta affects the architecture of the heart under both normal and pathological conditions. Moreover, TGF-beta signaling is currently under investigation, with the aim of discovering potential therapeutic roles in human disease. In contrast, only few studies have investigated whether TGF-beta affects electrophysiological properties of the heart. This fact is surprising since electrical remodeling represents an important substrate for cardiac disease. This review discusses the potential role of TGF-beta on cardiac excitation-contraction (EC) coupling, action potentials, and ion channels. We also discuss the effects of TGF-beta on cardiac development and disease from structural and electrophysiological points of view.

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Role of TGF-β on atrial remodeling. Certain physiological and pathophysiological conditions (ie, heart failure, rapid atrial rate of electrical stimulation, aging, and atrial dilatation) promotes the development of atrial fibrosis, which in turn provokes AF. Atrial fibrosis is developed in parallel to increased expression of TGF-β1, a well known profibrogenic agent. Interestingly, a compound named pirfenidone that exerts its biological actions by inhibiting the synthesis of TGF-β1, also prevents development of both atrial fibrosis and AF.41 This suggests a cause-effect relationship, by which TGF-β1 promotes development of atrial fibrosis, and thereby AF. Recent evidences obtained from cultured cells suggest thatTGF-β1 also provokes electrical remodeling (Table 1). These potentially in vivo electrophysiological effects by TGF-β1 could be attributed to a direct effect on ion channels expression and function (dotted arrow). Alternatively, they could be mediated by structural remolding (eg, fibrosis). Once established, electrical remodeling provokes AF and a vicious circle begins – termed atrial fibrillation begets atrial fibrillation, or AF begets AF.
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f3-vhrm-4-1289: Role of TGF-β on atrial remodeling. Certain physiological and pathophysiological conditions (ie, heart failure, rapid atrial rate of electrical stimulation, aging, and atrial dilatation) promotes the development of atrial fibrosis, which in turn provokes AF. Atrial fibrosis is developed in parallel to increased expression of TGF-β1, a well known profibrogenic agent. Interestingly, a compound named pirfenidone that exerts its biological actions by inhibiting the synthesis of TGF-β1, also prevents development of both atrial fibrosis and AF.41 This suggests a cause-effect relationship, by which TGF-β1 promotes development of atrial fibrosis, and thereby AF. Recent evidences obtained from cultured cells suggest thatTGF-β1 also provokes electrical remodeling (Table 1). These potentially in vivo electrophysiological effects by TGF-β1 could be attributed to a direct effect on ion channels expression and function (dotted arrow). Alternatively, they could be mediated by structural remolding (eg, fibrosis). Once established, electrical remodeling provokes AF and a vicious circle begins – termed atrial fibrillation begets atrial fibrillation, or AF begets AF.

Mentions: Atrial remodeling, which stands for “any persistent change in atrial structure or function”, promotes the occurrence or maintenance of atrial fibrillation (AF), by acting on the fundamental mechanisms of the arrhythmia (Thompson et al 1988). Accordingly, AF can be induced by several physiological and artificial stimuli (Figure 3), such as heart failure (Li et al 1999; Lee et al 2006), senescence (Anyukhovsky et al 2002; Hayashi et al 2002), atrial dilatation (Eckstein et al 2008), and rapid atrial rate of stimulation (Morillo et al 1995). Structural remodeling and in particular interstitial fibrosis represents the major promoter of AF. This is because fibrosis provokes disruption of electrical conduction among adjacent myocytes, due to an increased deposition of extracellular matrix, which disrupts the normal myocardial ultrastructure. In fact, transgenic mice overexpressing cardiac TGF-β1 develop atrial fibrosis, heterogeneous conduction, and AF (Verheule et al 2004). Additionally to atrial fibrosis, myocyte loss by either apoptosis or necrosis accompanies AF (Burstein and Nattel recently reviewed structural alterations associated to AF (Burstein and Nattel 2008)).


Role of TGF-beta on cardiac structural and electrical remodeling.

Ramos-Mondragón R, Galindo CA, Avila G - Vasc Health Risk Manag (2008)

Role of TGF-β on atrial remodeling. Certain physiological and pathophysiological conditions (ie, heart failure, rapid atrial rate of electrical stimulation, aging, and atrial dilatation) promotes the development of atrial fibrosis, which in turn provokes AF. Atrial fibrosis is developed in parallel to increased expression of TGF-β1, a well known profibrogenic agent. Interestingly, a compound named pirfenidone that exerts its biological actions by inhibiting the synthesis of TGF-β1, also prevents development of both atrial fibrosis and AF.41 This suggests a cause-effect relationship, by which TGF-β1 promotes development of atrial fibrosis, and thereby AF. Recent evidences obtained from cultured cells suggest thatTGF-β1 also provokes electrical remodeling (Table 1). These potentially in vivo electrophysiological effects by TGF-β1 could be attributed to a direct effect on ion channels expression and function (dotted arrow). Alternatively, they could be mediated by structural remolding (eg, fibrosis). Once established, electrical remodeling provokes AF and a vicious circle begins – termed atrial fibrillation begets atrial fibrillation, or AF begets AF.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2663446&req=5

f3-vhrm-4-1289: Role of TGF-β on atrial remodeling. Certain physiological and pathophysiological conditions (ie, heart failure, rapid atrial rate of electrical stimulation, aging, and atrial dilatation) promotes the development of atrial fibrosis, which in turn provokes AF. Atrial fibrosis is developed in parallel to increased expression of TGF-β1, a well known profibrogenic agent. Interestingly, a compound named pirfenidone that exerts its biological actions by inhibiting the synthesis of TGF-β1, also prevents development of both atrial fibrosis and AF.41 This suggests a cause-effect relationship, by which TGF-β1 promotes development of atrial fibrosis, and thereby AF. Recent evidences obtained from cultured cells suggest thatTGF-β1 also provokes electrical remodeling (Table 1). These potentially in vivo electrophysiological effects by TGF-β1 could be attributed to a direct effect on ion channels expression and function (dotted arrow). Alternatively, they could be mediated by structural remolding (eg, fibrosis). Once established, electrical remodeling provokes AF and a vicious circle begins – termed atrial fibrillation begets atrial fibrillation, or AF begets AF.
Mentions: Atrial remodeling, which stands for “any persistent change in atrial structure or function”, promotes the occurrence or maintenance of atrial fibrillation (AF), by acting on the fundamental mechanisms of the arrhythmia (Thompson et al 1988). Accordingly, AF can be induced by several physiological and artificial stimuli (Figure 3), such as heart failure (Li et al 1999; Lee et al 2006), senescence (Anyukhovsky et al 2002; Hayashi et al 2002), atrial dilatation (Eckstein et al 2008), and rapid atrial rate of stimulation (Morillo et al 1995). Structural remodeling and in particular interstitial fibrosis represents the major promoter of AF. This is because fibrosis provokes disruption of electrical conduction among adjacent myocytes, due to an increased deposition of extracellular matrix, which disrupts the normal myocardial ultrastructure. In fact, transgenic mice overexpressing cardiac TGF-β1 develop atrial fibrosis, heterogeneous conduction, and AF (Verheule et al 2004). Additionally to atrial fibrosis, myocyte loss by either apoptosis or necrosis accompanies AF (Burstein and Nattel recently reviewed structural alterations associated to AF (Burstein and Nattel 2008)).

Bottom Line: This fact is surprising since electrical remodeling represents an important substrate for cardiac disease.This review discusses the potential role of TGF-beta on cardiac excitation-contraction (EC) coupling, action potentials, and ion channels.We also discuss the effects of TGF-beta on cardiac development and disease from structural and electrophysiological points of view.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Bioquímica, Cinvestav-IPN, México.

ABSTRACT
The type beta transforming growth factors (TGF-betas) are involved in a number of human diseases, including heart failure and myocardial arrhythmias. In fact, during the last 20 years numerous studies have demonstrated that TGF-beta affects the architecture of the heart under both normal and pathological conditions. Moreover, TGF-beta signaling is currently under investigation, with the aim of discovering potential therapeutic roles in human disease. In contrast, only few studies have investigated whether TGF-beta affects electrophysiological properties of the heart. This fact is surprising since electrical remodeling represents an important substrate for cardiac disease. This review discusses the potential role of TGF-beta on cardiac excitation-contraction (EC) coupling, action potentials, and ion channels. We also discuss the effects of TGF-beta on cardiac development and disease from structural and electrophysiological points of view.

Show MeSH
Related in: MedlinePlus