bims-hafaim 2022-04-24 papers

Issue of 2022–04–24
three papers selected by
Kyle McCommis, Saint Louis University

Antioxidants (Basel). 2022 Apr 15. pii: 784. [Epub ahead of print]11(4):

Role of Oxidative Stress in Diabetic Cardiomyopathy.

Type 2 diabetes is a redox disease. Oxidative stress and chronic inflammation induce a switch of metabolic homeostatic set points, leading to glucose intolerance. Several diabetes-specific mechanisms contribute to prominent oxidative distress in the heart, resulting in the development of diabetic cardiomyopathy. Mitochondrial overproduction of reactive oxygen species in diabetic subjects is not only caused by intracellular hyperglycemia in the microvasculature but is also the result of increased fatty oxidation and lipotoxicity in cardiomyocytes. Mitochondrial overproduction of superoxide anion radicals induces, via inhibition of glyceraldehyde 3-phosphate dehydrogenase, an increased polyol pathway flux, increased formation of advanced glycation end-products (AGE) and activation of the receptor for AGE (RAGE), activation of protein kinase C isoforms, and an increased hexosamine pathway flux. These pathways not only directly contribute to diabetic cardiomyopathy but are themselves a source of additional reactive oxygen species. Reactive oxygen species and oxidative distress lead to cell dysfunction and cellular injury not only via protein oxidation, lipid peroxidation, DNA damage, and oxidative changes in microRNAs but also via activation of stress-sensitive pathways and redox regulation. Investigations in animal models of diabetic cardiomyopathy have consistently demonstrated that increased expression of the primary antioxidant enzymes attenuates myocardial pathology and improves cardiac function.

Keywords: HFpEF; HFrEF; apolipoprotein A-I; diabetic cardiomyopathy; heart failure; oxidative stress; pathological hypertrophy; pathological remodeling; primary antioxidant enzymes; type 2 diabetes mellitus

DOI: https://doi.org/10.3390/antiox11040784

Biomedicines. 2022 Mar 30. pii: 809. [Epub ahead of print]10(4):

Heart Failure Severity Closely Correlates with Intestinal Dysbiosis and Subsequent Metabolomic Alterations.

Martina E Spehlmann, Ashraf Y Rangrez, Dhiraj P Dhotre, Nesrin Schmiedel, Nikita Chavan, Corinna Bang, Oliver J Müller, Yogesh S Shouche, Andre Franke, Derk Frank, Norbert Frey.

Growing evidence suggests an altered gut microbiome in patients with heart failure (HF). However, the exact interrelationship between microbiota, HF, and its consequences on the metabolome are still unknown. We thus aimed here to decipher the association between the severity and progression of HF and the gut microbiome composition and circulating metabolites. Using a mouse model of transverse aortic constriction (TAC), gut bacterial diversity was found to be significantly lower in mice as early as day 7 post-TAC compared to Sham controls (p = 0.03), with a gradual progressive decrease in alpha-diversity on days 7, 14, and 42 (p = 0.014, p = 0.0016, p = 0.0021) compared to day 0, which coincided with compensated hypertrophy, maladaptive hypertrophy, and overtly failing hearts, respectively. Strikingly, segregated analysis based on the severity of the cardiac dysfunction (EF < 40% vs. EF 40-55%) manifested marked differences in the abundance and the grouping of several taxa. Multivariate analysis of plasma metabolites and bacterial diversity produced a strong correlation of metabolic alterations, such as reduced short-chain fatty acids and an increase in primary bile acids, with a differential abundance of distinct bacteria in HF. In conclusion, we showed that HF begets HF, likely via a vicious cycle of an altered microbiome and metabolic products.

Keywords: circulating metabolites; dysbiosis; gut microbiome; gut–heart axis; heart failure

DOI: https://doi.org/10.3390/biomedicines10040809

Diagnostics (Basel). 2022 Apr 14. pii: 989. [Epub ahead of print]12(4):

Sodium-Glucose Cotransporter-2 Inhibitors Improve Heart Failure with Reduced Ejection Fraction Outcomes by Reducing Edema and Congestion.

Michelle Hernandez, Ryan D Sullivan, Mariana E McCune, Guy L Reed, Inna P Gladysheva.

Pathological sodium-water retention or edema/congestion is a primary cause of heart failure (HF) decompensation, clinical symptoms, hospitalization, reduced quality of life, and premature mortality. Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) based therapies reduce hospitalization due to HF, improve functional status, quality, and duration of life in patients with HF with reduced ejection fraction (HFrEF) independently of their glycemic status. The pathophysiologic mechanisms and molecular pathways responsible for the benefits of SGLT-2i in HFrEF remain inconclusive, but SGLT-2i may help HFrEF by normalizing salt-water homeostasis to prevent clinical edema/congestion. In HFrEF, edema and congestion are related to compromised cardiac function. Edema and congestion are further aggravated by renal and pulmonary abnormalities. Treatment of HFrEF patients with SGLT-2i enhances natriuresis/diuresis, improves cardiac function, and reduces natriuretic peptide plasma levels. In this review, we summarize current clinical research studies related to outcomes of SGLT-2i treatment in HFrEF with a specific focus on their contribution to relieving or preventing edema and congestion, slowing HF progression, and decreasing the rate of rehospitalization and cardiovascular mortality.

Keywords: HFrEF; congestion; dilated cardiomyopathy; edema; endothelial dysfunction; fluid management

DOI: https://doi.org/10.3390/diagnostics12040989