The role of Perilipin 5 in pathological myocardial remodeling
Danzeng Dunzhu1, Gao Han2, Qin Shanshan1
1School of Medicine, Tibet University, Lhasa, China.
Insights
Perilipin 5 (Plin5) protein protects the heart from pathological cardiac remodeling by regulating lipid metabolism. Understanding Plin5
Area of Science:
- Cardiology
- Molecular Biology
- Metabolic Research
Background:
- Pathological cardiac remodeling (REM) is a key driver of heart failure (HF).
- REM involves cardiac tissue damage, altered energy metabolism, oxidative stress, and fibrosis.
- Current treatments for REM and HF have limitations.
Purpose of the Study:
- To review metabolic disorders linked to pathological cardiac remodeling.
- To investigate the role and regulatory mechanisms of Perilipin 5 (Plin5) in cardiac remodeling.
- To explore Plin5's function in modulating cardiac energy metabolism.
Main Methods:
- Systematic literature review.
- Analysis of current research on cardiac remodeling and lipid metabolism.
- Focus on Perilipin 5 (Plin5) properties and functions.
Main Results:
- Plin5 is crucial for regulating lipid droplet (LD) metabolism and fatty acid (FA) transport.
- Plin5 protects the heart by preventing excessive fatty acid oxidation.
- Plin5 plays a protective role against myocardial remodeling.
Conclusions:
- Plin5 is a key regulator of cardiac energy metabolism and a potential therapeutic target for heart failure.
- Modulating metabolic substrates, particularly via Plin5, may slow pathological cardiac remodeling.
- Further research into Plin5's molecular signaling is warranted for developing novel HF treatments.
Abstract:
Pathological cardiac remodeling (REM), caused by various pathological factors and characterized by changes in cardiac structure and geometry, is strongly associated with heart failure (HF). It damages cardiac tissue, alters energy metabolism, increases oxidative stress, and cause matrix metalloproteinase activation, cardiomyocyte hypertrophy, and interstitial fibrosis, leading to HF. REM determines the outcome of cardiovascular disease. Current treatments have limitations. REM is associated with cardiac energetic remodeling, and modulation of metabolic substrates may slow down the disease. Perilipin 5 (Plin5), positioned as a structural protein located on the surface of lipid droplets (LDs), is abundant in tissues and cells that rely on mitochondrial β-oxidation for energy production. It is the most recently identified member of the perilipin protein (PAT) family, with a notable enrichment in the cardiac muscle. Emerging evidence highlights the critical role of intracellular LD in the regulation of energy metabolism, with metabolic disruptions of LD being directly correlated with the incidence of metabolic disease. As a key barrier to LD, Plin5 is instrumental in controlling the catabolism of LD and regulating the metabolism and transport of fatty acids (FAs). As a protectant against excessive β-oxidation of free fatty acids (FFAs), Plin5 acts to isolate and neutralize overly oxidized fatty acids, thereby shielding the heart from myocardial remodeling instigated by a variety of etiological factors. This protective mechanism helps to ameliorate the progression of persistent and detrimental myocardial remodeling, which can otherwise lead to the development of severe heart failure. This systematic review attempts to delineate the metabolic disorders associated with pathological cardiac remodeling, focusing on the properties and regulatory mechanisms of Plin5. By synthesising current literature, it investigates the pivotal role of Plin5 in modulating the distinctive attributes, initiating factors, and molecular signaling networks underpinning pathological cardiac remodeling.
