Understanding the Role of SERCA2a Microdomain Remodeling in Heart Failure Induced by Obesity and Type 2 Diabetes
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Understanding the Role of SERCA2a Microdomain Remodeling in Heart Failure Induced by Obesity and Type 2 Diabetes. / Lai, Ping; Nikolaev, Viacheslav O; De Jong, Kirstie A.
in: J CARDIOVASC DEV DIS, Jahrgang 9, Nr. 5, 163, 19.05.2022.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Review › Forschung
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TY - JOUR
T1 - Understanding the Role of SERCA2a Microdomain Remodeling in Heart Failure Induced by Obesity and Type 2 Diabetes
AU - Lai, Ping
AU - Nikolaev, Viacheslav O
AU - De Jong, Kirstie A
PY - 2022/5/19
Y1 - 2022/5/19
N2 - Obesity and type 2 diabetes (T2D) are on trend to become a huge burden across all ages. They cause harm to almost every organ, especially the heart. For decades, the incidence of heart failure with impaired diastolic function (or called heart failure with preserved ejection fraction, HFpEF) has increased sharply. More and more studies have uncovered obesity and T2D to be closely associated with HFpEF. The sarcoplasmic/endoplasmic reticulum calcium ATPase2a (SERCA2a) microdomain is a key regulator of calcium reuptake into the sarcoplasmic reticulum (SR) during diastole. 3',5'-cyclic adenosine monophosphate (cAMP) and its downstream effector cAMP dependent protein kinase (PKA) act locally within the SERCA2a microdomain to regulate the phosphorylation state of the small regulatory protein phospholamban (PLN), which forms a complex with SERCA2a. When phosphorylated, PLN promotes calcium reuptake into the SR and diastolic cardiac relaxation by disinhibiting SERCA2a pump function. In this review, we will discuss previous studies investigating the PLN/SERCA2a microdomain in obesity and T2D in order to gain a greater understanding of the underlying mechanisms behind obesity- and T2D-induced diastolic dysfunction, with the aim to identify the current state of knowledge and future work that is needed to guide further research in the field.
AB - Obesity and type 2 diabetes (T2D) are on trend to become a huge burden across all ages. They cause harm to almost every organ, especially the heart. For decades, the incidence of heart failure with impaired diastolic function (or called heart failure with preserved ejection fraction, HFpEF) has increased sharply. More and more studies have uncovered obesity and T2D to be closely associated with HFpEF. The sarcoplasmic/endoplasmic reticulum calcium ATPase2a (SERCA2a) microdomain is a key regulator of calcium reuptake into the sarcoplasmic reticulum (SR) during diastole. 3',5'-cyclic adenosine monophosphate (cAMP) and its downstream effector cAMP dependent protein kinase (PKA) act locally within the SERCA2a microdomain to regulate the phosphorylation state of the small regulatory protein phospholamban (PLN), which forms a complex with SERCA2a. When phosphorylated, PLN promotes calcium reuptake into the SR and diastolic cardiac relaxation by disinhibiting SERCA2a pump function. In this review, we will discuss previous studies investigating the PLN/SERCA2a microdomain in obesity and T2D in order to gain a greater understanding of the underlying mechanisms behind obesity- and T2D-induced diastolic dysfunction, with the aim to identify the current state of knowledge and future work that is needed to guide further research in the field.
U2 - 10.3390/jcdd9050163
DO - 10.3390/jcdd9050163
M3 - SCORING: Review article
C2 - 35621874
VL - 9
JO - J CARDIOVASC DEV DIS
JF - J CARDIOVASC DEV DIS
SN - 2308-3425
IS - 5
M1 - 163
ER -