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Metabolic Cardiology
Published in Stephen T. Sinatra, Mark C. Houston, Nutritional and Integrative Strategies in Cardiovascular Medicine, 2022
The energy-starved heart is often not considered by physicians who treat cardiac disease on a day-to-day basis. Angiotensin-converting enzyme inhibitors and angiotensin receptor II blockers improve survival in ischemic and non-ischemic HFs and should be considered as a conventional approach in any patient with heart failure. However, therapies that target the cardiomyocyte itself must also be employed as it has been shown that cardiomyocytes in the failing heart, although metabolically compromised, and their function can be potentially improved and restored. Therapies that go beyond symptomatic relief (diuretics), and the neurohormonal axis, must also be considered that target the cellular, mitochondrial and metabolic defects. Metabolic support with D-ribose, CoQ10, L-carnitine and magnesium is critical for the maintenance of contractile reserve and energy charge in minimally oxidative ischemic or hypoxic hearts. Preservation of cellular energy charge provides the chemical driving force required to complete ATPase reactions needed to maintain cell and tissue viability and function. D-ribose, CoQ10, L-carnitine and magnesium exert a physiological benefit that has a positive impact on cardiac function.
High Carbohydrate Diet-Induced Metabolic Syndrome in the Overweight Body
Published in Nilanjana Maulik, Personalized Nutrition as Medical Therapy for High-Risk Diseases, 2020
Long-term MetS leads to multiorgan dysfunction, especially CVD, a major cause of mortality in modern society. MetS is very common in developed countries, and its prevalence is expected to further increase in the near future, in parallel with the rapidly increasing prevalence of obesity and T2D (Eckel, Barouch et al. 2002; Gallagher, Leroith et al. 2010; Dinh, Lankisch et al. 2011). Furthermore, these abnormalities are leading to the loss of cardiomyocytes, CVD and ultimately heart failure in humans (Hansen 1999; Mancia, Bombelli et al. 2010; Kassi, Pervanidou et al. 2011; Matsuzawa, Funahashi et al. 2011). In other words, MetS is the name for a group of factors that increases the risk of heart diseases and other health problems, such as diabetes and stroke. However, it is not very clear yet what is the exact relationship between MetS and development of cardiovascular disorders. Furthermore, MetS can induce increases in the risk for CVD in humans, but there are some contradictory finding in both humans and experimental animals. As an example, although it has been generally documented as a systematic metabolism complication in individuals with high sucrose in their daily diet, its direct cardiac effect cannot be clarified yet. Therefore, we need to know how MetS is affecting the population, as well as why personalized nutrition is applicable in managing it.
Regeneration of Cardiomyocytes from Bone Marrow Stem Cells and Application to Cell Transplantation Therapy
Published in Richard K. Burt, Alberto M. Marmont, Stem Cell Therapy for Autoimmune Disease, 2019
Cardiomyocytes in vivo respond to stimulation by both sympathetic and parasympathetic nerves, and such stimulation alters the heart rate, conduction velocity, and contractility, enabling the cells to adapt to rapid changes in systemic oxygen demand. To date, and to our knowledge, ES cells and mesenchymalstem-cell-derived CMG cells are the only possible candidates for regeneration of cardiomyocytes. We have already transplanted these cells into normal adult mouse hearts, and have observed that transplanted cells survived in recipient hearts for at least several weeks. Regenerated cardiomyocytes must express functional adrenergic and muscarinic receptors to be useful for transplantation, and although we did not investigate all signaling pathways and their functions, CMG cells are potential candidates for cardiomyocyte cell transplantation, because they possess such receptors.
Improving mitochondrial function in preclinical models of heart failure: therapeutic targets for future clinical therapies?
Published in Expert Opinion on Therapeutic Targets, 2023
Anna Gorący, Jakub Rosik, Joanna Szostak, Bartosz Szostak, Szymon Retfiński, Filip Machaj, Andrzej Pawlik
Heart failure is a complex clinical syndrome resulting from the unsuccessful compensation of symptoms of myocardial damage by several factors. Mitochondrial dysfunction is a process that occurs because of an attempt to adapt to the disruption of metabolic and energetic pathways occurring in the myocardium. This, in turn, leads to further dysfunction in cardiomyocyte processes. In the mitochondria, oxidation and reduction processes take place, generating the electrochemical gradients necessary for ATP synthesis. Mitochondrial energy metabolism is also a major source of ROS; therefore, it plays an important role in regulating oxidative stress. In addition to its key role in ATP synthesis and redox homeostasis, mitochondria are involved in numerous metabolic processes, in the oxidation of FA and amino acids, ion transport, and the synthesis of many other compounds that affect cardiomyocyte function [181,182].
Enzyme/pH dual stimuli-responsive nanoplatform co-deliver disulfiram and doxorubicin for effective treatment of breast cancer lung metastasis
Published in Expert Opinion on Drug Delivery, 2023
Peifu Xiao, Xiaoguang Tao, Hanxun Wang, Hongbing Liu, Yupeng Feng, Yueqi Zhu, Zhengzhen Jiang, Tian Yin, Yu Zhang, Haibing He, Jingxin Gou, Xing Tang
The weight changes of mice were monitored regularly during the experiment to evaluate the safety of NPs. Compared to the solution group, the body weight loss of the DSF-DOX NP group during administration was smaller, indicating that polymer nanoparticles significantly reduced systemic toxicity (Figure 9e). Apart from the DSF + DOX solution group that showed obvious myocardial toxicity, no apparent major organ injury was observed in other groups, which demonstrates the safety of these NPs (Figure 9f). The study measured well-established markers of biochemical damage to cardiomyocytes in both the heart and serum. The results showed that both DOX NPs and DSF-DOX NPs reduced the cardiotoxicity of the DOX solution, as indicated by the levels of damage-associated enzymes in serum (Fig. S4). Additionally, the content differences of cardiotoxicity markers in heart tissue (Fig. S5) also supported the inference that the NPs significantly reduced side effects.
Targeting calcium-mediated inter-organellar crosstalk in cardiac diseases
Published in Expert Opinion on Therapeutic Targets, 2022
Mohit M. Hulsurkar, Satadru K. Lahiri, Jason Karch, Meng C. Wang, Xander H.T. Wehrens
Cardiomyocytes are comprised of multiple organelles specialized in cellular functions such as protein synthesis and folding, ATP synthesis and metabolism, contractility, etc. While these organelles are separated by their own lipid bilayer membranes, there is a continuous crosstalk between them to facilitate and coordinate cellular functionality [1,2]. An increasing number of studies are providing insights into communication between different organelles [3], which can be mediated by secondary messengers such as calcium (Ca2+) or direct physical contact, such as mitochondria-associated membranes (MAMs) at the mitochondrial-endoplasmic/sarcoplasmic reticulum (ER/SR) interface [4]. This inter-organellar crosstalk is essential for coordinating the activities of various organelles and maintaining the overall function of cells [5–7].