Publications

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a protein crucial for cellular stress response and survival, particularly in the nervous and cardiovascular systems. Unlike traditional neurotrophic factors, MANF primarily regulates endoplasmic reticulum (ER) stress and protects cells by reducing ER stress-induced apoptosis. MANF operates both inside and outside cells, influencing key pathways like JAK/STAT and NF-κB to enhance cell survival during stress. Beyond its neuroprotective role, MANF is also vital in cardiovascular protection, mitigating damage by reducing inflammation and maintaining cellular function. Elevated MANF levels have been observed in patients experiencing myocardial infarction and murine models of ischemia-reperfusion (I/R) injury, highlighting its importance in these conditions. Overexpression of MANF in cardiomyocytes reduces ER-stress-induced cell death, while its depletion worsens this effect. Treatment with recombinant MANF (rMANF) has been shown to improve cardiac function in mice with I/R injury by decreasing infarct size and inflammation. Research also indicates that alterations in the α1-helix region of MANF can impact its structure, expression, secretion, and overall function. Given its protective effects and involvement in critical signaling pathways, MANF is being explored as a potential therapeutic target for ER stress-related diseases, including neurodegenerative disorders and cardiovascular conditions like myocardial I/R injury.

BACKGROUND: Recent studies conducted in COVID-19 survivors suggest that SARS-CoV-2 infection is associated with an increased risk of dyslipidemia. However, it remains unclear whether this augmented risk is confirmed in the general population and how this phenomenon is impacting the overall burden of cardiometabolic diseases.

METHODS: To address these aspects, we conducted a 6-year longitudinal study to examine the broader effects of COVID-19 on dyslipidemia incidence within a real-world population (228,266 subjects) residing in Naples, Southern Italy. The pre-COVID-19 and the COVID-19 groups were balanced for demographic and clinical factors using propensity score matching.

RESULTS: Our analysis spans over a period of three years during the pandemic (2020-2022), comparing dyslipidemia incidence with pre-pandemic data (2017-2019), with a follow-up time of at least 1,095 days corresponding to 21,349,215 person-years. During the COVID-19 period we detected an increased risk of developing any dyslipidemia when compared with the pre-COVID-19 triennium (OR = 1.29, 95% CI 1.19-1.39). Importantly, these estimates were adjusted for comorbidities by a multivariate analysis.

CONCLUSIONS: Taken together, our data reveal a notable rise in dyslipidemia incidence amid the COVID-19 pandemic, suggesting to establish specialized clinical monitoring protocols for COVID-19 survivors to mitigate the risk of dyslipidemia development.

Aging represents a complex biological progression affecting the entire body, marked by a gradual decline in tissue function, rendering organs more susceptible to stress and diseases. The human heart holds significant importance in this context, as its aging process poses life-threatening risks. It entails macroscopic morphological shifts and biochemical changes that collectively contribute to diminished cardiac function. Among the numerous pivotal factors in aging, mitochondria play a critical role, intersecting with various molecular pathways and housing several aging-related agents. In this comprehensive review, we provide an updated overview of the functional role of mitochondria in cardiac aging.