Savino, Marco, Luigi Savino, Pasquale Mone, Concetta Schiano, Antonio De Luca, and Gaetano Santulli. (2024) 2024. “Predicting Exercise Intolerance in Elderly Individuals With Heart Failure Using the 30-Second Chair Stand Test”. International Journal of Cardiology. Heart & Vasculature 53: 101464. https://doi.org/10.1016/j.ijcha.2024.101464.
Mone, Pasquale, Esther Densu Agyapong, Giampaolo Morciano, Stanislovas S Jankauskas, Antonio De Luca, Fahimeh Varzideh, Paolo Pinton, and Gaetano Santulli. (2024) 2024. “Dysfunctional Mitochondria Elicit Bioenergetic Decline in the Aged Heart”. The Journal of Cardiovascular Aging 4 (2). https://doi.org/10.20517/jca.2023.50.
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.
Buonaiuto, Antonietta, Jessica Gambardella, Gaetano Santulli, Antonella Fiordelisi, Xujun Wang, Nella Prevete, Edoardo Sommella, et al. (2024) 2024. “Macrophages Release MiRNAs in Response to Doxorubicin With a Potential Role in Indirect Cardiac Damage”. Vascular Pharmacology 155: 107302. https://doi.org/10.1016/j.vph.2024.107302.
Gambardella, Jessica, Antonella Fiordelisi, Federica Andrea Cerasuolo, Antonietta Buonaiuto, Roberta Avvisato, Alessandro Viti, Eduardo Sommella, et al. (2024) 2024. “Early Impairment in Mitochondrial Quality Check and Function Precedes the Development of Cardiac Phenotypes in an Mouse Model of Fabry Disease”. Vascular Pharmacology 155: 107320. https://doi.org/10.1016/j.vph.2024.107320.
Gambardella, Jessica, Stanislovas S Jankauskas, Urna Kansakar, Fahimeh Varzideh, Roberta Avvisato, and Gaetano Santulli. (2024) 2024. “COVID-19 Causes the Opening of the Mitochondrial Permeability Transition Pore in Human Endothelial Cells”. Vascular Pharmacology 155: 107349. https://doi.org/10.1016/j.vph.2024.107349.
Bromelain is a mixture of proteolytic enzymes primarily extracted from the fruit and stem of the pineapple plant (Ananas comosus). It has a long history of traditional medicinal use in various cultures, particularly in Central and South America, where pineapple is native. This systematic review will delve into the history, structure, chemical properties, and medical indications of bromelain. Bromelain was first isolated and described in the late 19th century by researchers in Europe, who identified its proteolytic properties. Since then, bromelain has gained recognition in both traditional and modern medicine for its potential therapeutic effects.
Avvisato, Roberta, Stanislovas S Jankauskas, Pasquale Mone, Urna Kansakar, Fahimeh Varzideh, Stefano De Gennaro, Luigi Salemme, et al. (2024) 2024. “MiR-181c Modulates SMAD7 and Parkin in Human Cardiac Fibroblasts: Validation in Frail Older Adults With Diabetes and HFpEF”. Vascular Pharmacology 155: 107350. https://doi.org/10.1016/j.vph.2024.107350.
Jankauskas, Stanislovas S, Fahimeh Varzideh, Urna Kansakar, Ghaith Al Tibi, Esther Densu Agyapong, Jessica Gambardella, and Gaetano Santulli. (2024) 2024. “Insights into Molecular and Cellular Functions of the Golgi Calcium/Manganese-Proton Antiporter TMEM165”. The Journal of Biological Chemistry 300 (8): 107567. https://doi.org/10.1016/j.jbc.2024.107567.
The Golgi compartment performs a number of crucial roles in the cell. However, the exact molecular mechanisms underlying these actions are not fully defined. Pathogenic mutations in genes encoding Golgi proteins may serve as an important source for expanding our knowledge. For instance, mutations in the gene encoding Transmembrane protein 165 (TMEM165) were discovered as a cause of a new type of congenital disorder of glycosylation (CDG). Comprehensive studies of TMEM165 in different model systems, including mammals, yeast, and fish uncovered the new realm of Mn2+ homeostasis regulation. TMEM165 was shown to act as a Ca2+/Mn2+:H+ antiporter in the medial- and trans-Golgi network, pumping the metal ions into the Golgi lumen and protons outside. Disruption of TMEM165 antiporter activity results in defects in N- and O-glycosylation of proteins and glycosylation of lipids. Impaired glycosylation of TMEM165-CDG arises from a lack of Mn2+ within the Golgi. Nevertheless, Mn2+ insufficiency in the Golgi is compensated by the activity of the ATPase SERCA2. TMEM165 turnover has also been found to be regulated by Mn2+ cytosolic concentration. Besides causing CDG, recent investigations have demonstrated the functional involvement of TMEM165 in several other pathologies including cancer and mental health disorders. This systematic review summarizes the available information on TMEM165 molecular structure, cellular function, and its roles in health and disease.
Ischemia with non-obstructive coronary artery (INOCA) is a common cause of hospital admissions, leading to negative outcomes and reduced quality of life. Central to its pathophysiology is endothelial dysfunction, which contributes to myocardial ischemia despite the absence of significant coronary artery blockage. Addressing endothelial dysfunction is essential in managing INOCA to alleviate symptoms and prevent cardiovascular events. Recent studies have identified diabetes mellitus (DM) as a significant factor exacerbating INOCA complications by promoting endothelial impairment and coronary microvascular dysfunction. MicroRNAs (miRNAs) have emerged as potential biomarkers and therapeutic targets in various biological processes, including endothelial dysfunction and cardiovascular diseases. However, research on miRNA biomarkers in INOCA patients is sparse. In this study, we examined a panel of circulating miRNAs involved in the regulation of endothelial function in INOCA patients with and without DM. We analyzed miRNA expression using RT-qPCR in a cohort of consecutive INOCA patients undergoing percutaneous coronary intervention. We detected a significant dysregulation of miR-363-5p and miR-92a-3p in INOCA patients with DM compared to those without DM, indicating their role as biomarkers for predicting and monitoring endothelial dysfunction in INOCA patients with DM.
Santulli, Gaetano, Marco Savino, Klara Komici, Pasquale Mone, Luigi Savino, and Stanislovas S Jankauskas. (2024) 2024. “A Novel Imaging Marker for Asymptomatic Cerebrovascular Lesions in Hypertension”. American Journal of Hypertension. https://doi.org/10.1093/ajh/hpae100.
Mone, Pasquale, Leonardo Bencivenga, Gaetano Santulli, Giuseppe Rengo, Germano Guerra, and Klara Komici. (2024) 2024. “Time to Negative Conversion and Cardiopulmonary Performance in Athletes With COVID-19”. ERJ Open Research 10 (4). https://doi.org/10.1183/23120541.00090-2024.
Athletes with longer time to negative conversion for COVID-19 do not present reduction of exercise capacity. However, respiratory and ventilatory parameters are modified. https://bit.ly/3TMdrFL.
Savino, Luigi, Marco Savino, Urna Kansakar, Tommaso Dazzetti, Fahimeh Varzideh, Stanislovas S Jankauskas, Pasquale Mone, and Gaetano Santulli. (2024) 2024. “Extracellular RNA and Endothelial TLR3 Link Inflammation and Venous Thromboembolism”. Journal of the American Heart Association 13 (15): e036335. https://doi.org/10.1161/JAHA.124.036335.
Recent research has sparked increasing interest in the effects of dietary supplements on cardiovascular and metabolic disorders [...].
Lembo, Maria, Valentina Trimarco, Raffaele Izzo, Maria Virginia Manzi, Francesco Rozza, Paola Gallo, Carmine Morisco, et al. (2024) 2024. “Achieving a Systolic Blood Pressure Below 130 MmHg Reduces the Incidence of Cardiovascular Events in Hypertensive Patients With Echocardiographic Left Ventricular Hypertrophy”. The Journal of Pharmacology and Experimental Therapeutics 390 (1): 4-10. https://doi.org/10.1124/jpet.123.001952.
Background: Recent reports have evidenced an increased mortality rate in hypertensive patients with electrocardiographic left ventricular hypertrophy (ECG-LVH) achieving systolic blood pressure (SBP) <130 mmHg. However, to the best of our knowledge, the actual effects of blood pressure reduction to the ≤130/80 mmHg target on the incidence of cardiovascular (CV) events have never been determined in hypertensive patients with a diagnosis of left ventricular hypertrophy based on echocardiographic criteria (Echo-LVH). Methods: To fill this long-standing knowledge gap, we harnessed a population of 9511 hypertensive patients, followed-up for 33.6 [interquartile range 7.9-72.7] months. The population was divided into six groups according to the average SBP achieved during the follow-up (≤130, 130-139, and ≥140 mmHg) and absence/presence of Echo-LVH. The primary endpoint was a composite of fatal or nonfatal myocardial infarction and stroke, sudden cardiac death, heart failure requiring hospitalization, revascularization, and carotid stenting. Secondary endpoints included atrial fibrillation and transient ischemic attack. Results: During the follow-up, achieved SBP and diastolic blood pressure (DBP) were comparable between patients with and without Echo-LVH. Strikingly, the rates of primary and secondary endpoints were significantly higher in patients with Echo-LVH and SBP >130 mmHg, reaching the highest values in the Echo-LVH group with SBP ≥140 mmHg. By separate Cox multivariable regressions, after adjusting for potential confounders, both primary and secondary endpoints were significantly associated with SBP ≥140 mmHg and Echo-LVH. Instead, DBP reduction ≤80 mmHg was associated with a significant increased rate of secondary events. Conclusions: In hypertensive patients with Echo-LVH, achieving an average in-treatment SBP target ≤130 mmHg has a beneficial prognostic impact on incidence of CV events. SIGNIFICANCE STATEMENT: Contrary to recent findings, achieving in-treatment SBP ≤130 mmHg lowers the incidence of CV events in hypertensive patients with Echo-LVH. However, reducing DBP ≤80 mmHg is linked to increased CV complications. Cox multivariable regression models, considering potential confounders, reveal that the rate of hard and soft CV events is significantly associated with Echo-LVH and SBP ≥140 mmHg. Our data indicate that therapeutic strategies for Echo-LVH patients should target SBP ≤130 mmHg while avoiding lowering DBP ≤80 mmHg.
BACKGROUND: Prediabetes has garnered increasing attention due to its association with cardiovascular conditions, especially hypertension, which heightens the risk of prefrailty and frailty among older individuals.
METHODS: We screened elders with prefrail hypertension from March 2021 to January 2023. We assessed the correlation linking cognitive dysfunction (Montreal Cognitive Assessment score), insulin resistance (triglyceride-to-glucose index), and physical impairment (5-meter gait speed). Then, we measured the risk of developing frailty after a 1-year follow-up period, adjusting the outcome using multivariable Cox regression analysis. We also investigated the impact of administering 500 mg of metformin once daily to a subset of frail subjects for an additional 6 months.
RESULTS: We assessed the relationship between the triglyceride-to-glucose index and the Montreal Cognitive Assessment score, observing a significant correlation (r, 0.880; P<0.0001). Similarly, we analyzed the association between the triglyceride-to-glucose index and 5-meter gait speed, uncovering a significant link between insulin resistance and physical impairment (r, 0.809; P<0.0001). Prediabetes was found to significantly (P<0.0001) elevate the risk of frailty development compared with individuals without prediabetes by the end of the 1-year follow-up, a finding confirmed via multivariable analysis with Cox regression. Furthermore, among the subgroup of subjects who developed frailty, those who received metformin exhibited a significant decrease in frailty levels (P<0.0001).
CONCLUSIONS: Insulin resistance and prediabetes play substantial roles in the development of cognitive and physical impairments, highlighting their importance in managing hypertension, even before the onset of frank diabetes. Metformin, a well-established drug for the treatment of diabetes, has shown favorable effects in mitigating frailty.
Santulli, Gaetano, Valeria Visco, Michele Ciccarelli, Mario Nicola Vittorio Ferrante, Piero De Masi, Antonella Pansini, Nicola Virtuoso, et al. (2024) 2024. “Frail Hypertensive Older Adults With Prediabetes and Chronic Kidney Disease: Insights on Organ Damage and Cognitive Performance - Preliminary Results from the CARYATID Study”. Cardiovascular Diabetology 23 (1): 125. https://doi.org/10.1186/s12933-024-02218-x.
BACKGROUND: Hypertension and chronic kidney disease (CKD) pose significant public health challenges, sharing intertwined pathophysiological mechanisms. Prediabetes is recognized as a precursor to diabetes and is often accompanied by cardiovascular comorbidities such as hypertension, elevating the risk of pre-frailty and frailty. Albuminuria is a hallmark of organ damage in hypertension amplifying the risk of pre-frailty, frailty, and cognitive decline in older adults. We explored the association between albuminuria and cognitive impairment in frail older adults with prediabetes and CKD, assessing cognitive levels based on estimated glomerular filtration rate (eGFR).
METHODS: We conducted a study involving consecutive frail older patients with hypertension recruited from March 2021 to March 2023 at the ASL (local health unit of the Italian Ministry of Health) of Avellino, Italy, followed up after three months. Inclusion criteria comprised age over 65 years, prior diagnosis of hypertension without secondary causes, prediabetes, frailty status, Montreal Cognitive Assessment (MoCA) score < 26, and CKD with eGFR > 15 ml/min.
RESULTS: 237 patients completed the study. We examined the association between albuminuria and MoCA Score, revealing a significant inverse correlation (r: 0.8846; p < 0.0001). Subsequently, we compared MoCA Score based on eGFR, observing a significant difference (p < 0.0001). These findings were further supported by a multivariable regression analysis, with albuminuria as the dependent variable.
CONCLUSIONS: Our study represents the pioneering effort to establish a significant correlation between albuminuria and eGFR with cognitive function in frail hypertensive older adults afflicted with prediabetes and CKD.
Trimarco, Valentina, Raffaele Izzo, Daniela Pacella, Ugo Trama, Maria Virginia Manzi, Angela Lombardi, Roberto Piccinocchi, et al. (2024) 2024. “Incidence of New-Onset Hypertension Before, During, and After the COVID-19 Pandemic: A 7-Year Longitudinal Cohort Study in a Large Population”. BMC Medicine 22 (1): 127. https://doi.org/10.1186/s12916-024-03328-9.
BACKGROUND: While the augmented incidence of diabetes after COVID-19 has been widely confirmed, controversial results are available on the risk of developing hypertension during the COVID-19 pandemic.
METHODS: We designed a longitudinal cohort study to analyze a closed cohort followed up over a 7-year period, i.e., 3 years before and 3 years during the COVID-19 pandemic, and during 2023, when the pandemic was declared to be over. We analyzed medical records of more than 200,000 adults obtained from a cooperative of primary physicians from January 1, 2017, to December 31, 2023. The main outcome was the new diagnosis of hypertension.
RESULTS: We evaluated 202,163 individuals in the pre-pandemic years and 190,743 in the pandemic years, totaling 206,857 when including 2023 data. The incidence rate of new hypertension was 2.11 (95% C.I. 2.08-2.15) per 100 person-years in the years 2017-2019, increasing to 5.20 (95% C.I. 5.14-5.26) in the period 2020-2022 (RR = 2.46), and to 6.76 (95% C.I. 6.64-6.88) in 2023. The marked difference in trends between the first and the two successive observation periods was substantiated by the fitted regression lines of two Poisson models conducted on the monthly log-incidence of hypertension.
CONCLUSIONS: We detected a significant increase in new-onset hypertension during the COVID-19 pandemic, which at the end of the observation period affected 20% of the studied cohort, a percentage higher than the diagnosis of COVID-19 infection within the same time frame. This observation suggests that increased attention to hypertension screening should not be limited to individuals who are aware of having contracted the infection but should be extended to the entire population.
Patent Foramen Ovale (PFO) is a remnant of fetal circulation that could be observed in the 25% of the population worldwide. PFO is associated to numerous clinical conditions as migraines, coronary embolization, transient ischemic attacks, and stroke. The main PFO concerns are related to its correlation to stroke, in particular in young adults. Despite the impact on morbidity that PFO could have, to date there is not clear evidence about its management and treatment. In this narrative review our aim is to summarize the more recent evidence in the literature dealing with PFO, in order to provide an updated overview on this topic.
Mone, Pasquale, Antonio De Luca, and Gaetano Santulli. (2023) 2023. “Editorial: Frailty and Oxidative Stress”. Frontiers in Aging 4: 1345486. https://doi.org/10.3389/fragi.2023.1345486.