Metabolic Reprogramming, Gut Dysbiosis, and Nutrition Intervention in Canine Heart Disease

Abstract

This review provides a state-of-the-art overview on recent advances in systems biology in canine cardiac disease, with a focus on our current understanding of bioenergetics and amino acid metabolism in myxomatous mitral valve disease (MMVD). Cross-species comparison is drawn to highlight the similarities between human and canine heart diseases. The adult mammalian heart exhibits a remarkable metabolic flexibility and shifts its energy substrate preference according to different physiological and pathological conditions. The failing heart suffers up to 40% ATP deficit and is compared to an engine running out of fuel. Bioenergetics and metabolic readaptations are among the major research topics in cardiac research today. Myocardial energy metabolism consists of three interconnected components: substrate utilization, oxidative phosphorylation, and ATP transport and utilization. Any disruption or uncoupling of these processes can result in deranged energy metabolism leading to heart failure (HF). The review describes the changes occurring in each of the three components of energy metabolism in MMVD and HF. It also provides an overview on the changes in circulating and myocardial glutathione, taurine, carnitines, branched-chain amino acid catabolism and tryptophan metabolic pathways. In addition, the review summarizes the potential role of the gut microbiome in MMVD and HF. As our knowledge and understanding in these molecular and metabolic processes increase, it becomes possible to use nutrition to address these changes and to slow the progression of the common heart diseases in dogs.

RNA sequencing provides novel insights into the pathogenesis of naturally occurring myxomatous mitral valve disease stage B1 in beagle dogs

“…KEGG pathway analysis revealed significant differences in gene expression between the NC and MMVD groups, emphasizing the importance of metabolic pathways. Dysfunctional metabolic pathways, when altered pathologically, lead to impaired signal transmission and disruptions in energy and redox balance, ultimately causing contractile dysfunction in the diseased heart [ 69 ]. This indicates the existence of notable changes in metabolic activity between the MMVD and NC groups.…”

Combined analysis of plasma metabolome and intestinal microbiome sequencing to explore jiashen prescription and its potential role in changing intestine–heart axis and effect on chronic heart failure

“…As the main component of human and animal intestinal microflora, the normal growth of these bacteria depended on porphyrins, including protoporphyrin IX or heme with iron (55) (Figure 8). Kynurenine (C01717), a metabolite of the L-tryptophan pathway, may mediate immunomodulation, oxidant defense, and apoptosis (56), which are considered pathogenic features in the development of heart failure, and has been shown to predict cardiovascular events (57,58). Similarly, PE (18:0/0:0) (C21484) participated in the process of lipid peroxidation (LPO) in the pathway of ferroptosis.…”

“…Similarly, PE (18:0/0:0) (C21484) participated in the process of lipid peroxidation (LPO) in the pathway of ferroptosis. LPO which is one of their metabolites is involved in immune responses and cell deaths (58,59). Kynurenine and PE (18:0/0:0) were significantly correlated with the abundance of 10 and 49 species of bacteria, respectively, in this research.…”

Defisiensi Mikronutrien pada Gagal Jantung: Disfungsi Mitokondrial sebagai Patofisiologi

“…Dengan demikian, impermeabilitas membran bagian dalam dan potensi membran mitokondria menjadi bagian yang penting dari fungsi mitokondria. 3,6 Mitokondria memiliki dampak langsung dan tidak langsung pada fisiologi kardiomiosit dengan mengatur bioenergi (kardiomiosit memiliki kebutuhan tinggi untuk sintesis ATP dan konsumsi oksigen), pensinyalan redoks (respon fisiologis), stres oksidatif (respon patologis), penanganan kalsium, sifat kontraktilitas, nekrosis dan apoptosis. Oleh karena itu, pemeliharaan fungsi dan integritas mitokondria jantung sangat penting untuk kesehatan manusia.…”