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Published on: March 25, 2020
Cholesterol Homeostasis, Mechanisms of Molecular Pathways, and Cardiac Health: A Current Outlook
Rajiv Kumar1, Neelam Chhillar2, Dhruv Sanjay Gupta3
1University of Delhi, Delhi, India.
Insights
Cholesterol metabolism impacts heart health by influencing cardiac remodeling. Understanding these links, including oxidative stress and energy pathways, is key to developing new treatments for heart failure.
Area of Science:
- Cardiovascular Biology
- Metabolic Regulation
- Molecular Medicine
Background:
- Lipoprotein metabolism is vital for cholesterol homeostasis and lipid transport.
- Cardiac remodeling involves molecular and cellular changes affecting heart structure and function after injury.
- Acetyl coenzyme A (acetyl CoA) is a key precursor for cholesterol synthesis.
Purpose of the Study:
- To explain the concepts of cardiac remodeling, its clinical implications, and pathophysiological roles.
- To explore the mechanisms of cholesterol regulation, including transcriptional control by SREBP.
- To review the pharmacological management and therapeutic targets for cardiac remodeling.
Main Methods:
- Review of existing literature on cardiac remodeling and cholesterol metabolism.
- Explanation of molecular and cellular mechanisms involved in heart disease.
- Discussion of immune cell activation and metabolic reprogramming in response to injury.
Main Results:
- Oxidative stress, impaired calcium handling, and cardiac fibrosis are primary drivers of heart failure progression.
- Metabolic reprogramming of catabolic and anabolic pathways is crucial for immune responses and energy production.
- Cholesterol homeostasis is maintained through de novo production, intestinal absorption, and biliary output.
Conclusions:
- Dysregulation of cholesterol metabolism and cardiac remodeling contribute significantly to heart disease.
- Targeting metabolic pathways and oxidative stress offers potential therapeutic strategies for cardiac remodeling.
- Further research into cholesterol absorption and its therapeutic targets is warranted.
Abstract:
The metabolism of lipoproteins, which regulate the transit of the lipid to and from tissues, is crucial to maintaining cholesterol homeostasis. Cardiac remodeling is referred to as a set of molecular, cellular, and interstitial changes that, following injury, affect the size, shape, function, mass, and geometry of the heart. Acetyl coenzyme A (acetyl CoA), which can be made from glucose, amino acids, or fatty acids, is the precursor for the synthesis of cholesterol. In this article, the authors explain concepts behind cardiac remodeling, its clinical ramifications, and the pathophysiological roles played by numerous various components, such as cell death, neurohormonal activation, oxidative stress, contractile proteins, energy metabolism, collagen, calcium transport, inflammation, and geometry. The levels of cholesterol are traditionally regulated by 2 biological mechanisms at the transcriptional stage. First, the SREBP transcription factor family regulates the transcription of crucial rate-limiting cholesterogenic and lipogenic proteins, which in turn limits cholesterol production. Immune cells become activated, differentiated, and divided, during an immune response with the objective of eradicating the danger signal. In addition to creating ATP, which is used as energy, this process relies on metabolic reprogramming of both catabolic and anabolic pathways to create metabolites that play a crucial role in regulating the response. Because of changes in signal transduction, malfunction of the sarcoplasmic reticulum and sarcolemma, impairment of calcium handling, increases in cardiac fibrosis, and progressive loss of cardiomyocytes, oxidative stress appears to be the primary mechanism that causes the transition from cardiac hypertrophy to heart failure. De novo cholesterol production, intestinal cholesterol absorption, and biliary cholesterol output are consequently crucial processes in cholesterol homeostasis. In the article's final section, the pharmacological management of cardiac remodeling is explored. The route of treatment is explained in different steps: including, promising, and potential strategies. This chapter offers a brief overview of the history of the study of cholesterol absorption as well as the different potential therapeutic targets.
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