Sandra Rodríguez-López

Bio: Sandra Rodríguez-López is an academic researcher from University of Córdoba (Spain). The author has contributed to research in topics: Medicine & Skeletal muscle. The author has an hindex of 2, co-authored 4 publications receiving 53 citations.

Mitochondrial adaptations in liver and skeletal muscle to pro-longevity nutritional and genetic interventions: the crosstalk between calorie restriction and CYB5R3 overexpression in transgenic mice.

Abstract: Calorie restriction without malnutrition (CR) is considered as the most effective nongenetic nor pharmacological intervention that promotes healthy aging phenotypes and can extend lifespan in most model organisms. Lifelong CR leads to an increase of cytochrome b5 reductase-3 (CYB5R3) expression and activity. Overexpression of CYB5R3 confers some of the salutary effects of CR, although the mechanisms involved might be independent because key aspects of energy metabolism and lipid profiles of tissues go in opposite ways. It is thus important to study if some of the metabolic adaptations induced by CR are affected by CYB5R3 overexpression. CYB5R3 overexpression greatly preserved body and liver weight in mice under CR conditions. In liver, CR did not modify mitochondrial abundance, but lead to increased expression of mitofusin Mfn2 and TFAM, a transcription factor involved in mitochondrial biogenesis. These changes were prevented by CYB5R3 overexpression but resulted in a decreased expression of a different mitochondrial biogenesis-related transcription factor, Nrf1. In skeletal muscle, CR strongly increased mitochondrial mass, mitofusin Mfn1, and Nrf1. However, CYB5R3 mice on CR did not show increase in muscle mitochondrial mass, regardless of a clear increase in expression of TFAM and mitochondrial complexes in this tissue. Our results support that CYB5R3 overexpression significantly modifies the metabolic adaptations of mice to CR.

Regulation of hepatic coenzyme Q biosynthesis by dietary omega-3 polyunsaturated fatty acids.

Abstract: Dietary fats are important for human health, yet it is not fully understood how different fats affect various health problems. Although polyunsaturated fatty acids (PUFAs) are generally considered as highly oxidizable, those of the n-3 series can ameliorate the risk of many age-related disorders. Coenzyme Q (CoQ) is both an essential component of the mitochondrial electron transport chain and the only lipid-soluble antioxidant that animal cells can synthesize. Previous work has documented the protective antioxidant properties of CoQ against the autoxidation products of PUFAs. Here, we have explored in vitro and in vivo models to better understand the regulation of CoQ biosynthesis by dietary fats. In mouse liver, PUFAs increased CoQ content, and PUFAs of the n-3 series increased preferentially CoQ10. This response was recapitulated in hepatic cells cultured in the presence of lipid emulsions, where we additionally demonstrated a role for n-3 PUFAs as regulators of CoQ biosynthesis via the upregulation of several COQ proteins and farnesyl pyrophosphate levels. In both models, n-3 PUFAs altered the mitochondrial network without changing the overall mitochondrial mass. Furthermore, in cellular systems, n-3 PUFAs favored the synthesis of CoQ10 over CoQ9, thus altering the ratio between CoQ isoforms through a mechanism that involved downregulation of farnesyl diphosphate synthase activity. This effect was recapitulated by both siRNA silencing and by pharmacological inhibition of farnesyl diphosphate synthase with zoledronic acid. We highlight here the ability of n-3 PUFAs to regulate CoQ biosynthesis, CoQ content, and the ratio between its isoforms, which might be relevant to better understand the health benefits associated with this type of fat. Additionally, we identify for the first time zoledronic acid as a drug that inhibits CoQ biosynthesis, which must be also considered with respect to its biological effects on patients.

The genetic background shapes the susceptibility to mitochondrial dysfunction and NASH progression

Abstract: Mice from different genetic backgrounds have widely diverse responses to the same metabolic challenges. Only PWK/PhJ mice show significant mitochondrial dysfunction and progression to fibrotic NASH that resembles human NASH. The PWK/PhJ strain is a novel NASH mouse model.

Patients with COVID-19: in the dark-NETs of neutrophils.

Abstract: SARS-CoV-2 infection poses a major threat to the lungs and multiple other organs, occasionally causing death. Until effective vaccines are developed to curb the pandemic, it is paramount to define the mechanisms and develop protective therapies to prevent organ dysfunction in patients with COVID-19. Individuals that develop severe manifestations have signs of dysregulated innate and adaptive immune responses. Emerging evidence implicates neutrophils and the disbalance between neutrophil extracellular trap (NET) formation and degradation plays a central role in the pathophysiology of inflammation, coagulopathy, organ damage, and immunothrombosis that characterize severe cases of COVID-19. Here, we discuss the evidence supporting a role for NETs in COVID-19 manifestations and present putative mechanisms, by which NETs promote tissue injury and immunothrombosis. We present therapeutic strategies, which have been successful in the treatment of immunο-inflammatory disorders and which target dysregulated NET formation or degradation, as potential approaches that may benefit patients with severe COVID-19.

Novel findings in neutrophil biology and their impact on cardiovascular disease.

Abstract: Neutrophils are the most abundant circulating leucocytes in healthy humans. These cells are central players during acute inflammatory responses, although a growing body of evidence supports a crucial role in chronic inflammation and chemokines and cytokines related to it as well. Thus, both humoral and cellular components are involved in the development of plaque formation and atherosclerosis. Accordingly, CANTOS trial using an interleukin-1 beta antibody confirmed that inflammatory cytokines contribute to the occurrence of myocardial infarction and cardiac death independent of changes in lipids. Recent data revealed that neutrophils are a heterogeneous population with different subsets and functional characteristics (i.e. CD177+ cells, OLFM4+ neutrophils, proangiogenic neutrophils, neutrophils undergoing reverse migration, and aged neutrophils). Importantly, neutrophils are able to synthesize de novo proteins. Neutrophil extracellular trap generation and NETosis have been considered as very important weapons in sterile inflammation. Neutrophil-derived microvesicles represent another mechanism by which neutrophils amplify inflammatory processes, being found at high levels both at the site of injury and in the bloodstream. Finally, neutrophil aging can influence their functions also in relation with host age. These recent acquisitions in the field of neutrophil biology might pave the way for new therapeutic targets to prevent or even treat patients experiencing cardiovascular (CV) diseases. Here, we discuss novel findings in neutrophil biology, their impact on CV and cerebrovascular diseases, and the potential implementation of these notions into daily clinical practice.