Protective Activity of Resveratrol in Cardio- and Cerebrovascular Diseases

Resveratrol (RSV) is a natural nonflavonoid polyphenol compound containing a stilbene structure similar to that of estrogen diethylstilbestrol. It is a fat-soluble compound existing in cis-, trans-, and piceid isomeric forms, isolated for the first time in 1940 from a plant used in traditional Chinese and Japanese medicine. Although initially used for cancer therapy, it has shown beneficial effects against most cardiovascular and cerebrovascular diseases. Its beneficial effects are mainly related to its antioxidant properties. Here, we review the metabolism and the ability of RSV to modulate redox signaling and to interact with multiple molecular targets of different intracellular pathways exerting protective effects against cardio-cerebrovascular diseases and metabolic disorders such as diabetes, reporting evidence in animal models and its efficacy and toxicity in humans. The aim of this chapter is to highlight the mechanisms, the biology, and the potential use of resveratrol to prevent, protect and aid cardio- and cerebrovascular diseases

It is easy to see, but it is better to foresee: a case report on the favourable alliance between CardioMEMS and levosimendan

Abstract Background In the past years, different devices have been investigated to help in identifying early decompensation events in patients with heart failure (HF) and reduced ejection fraction (EF), reducing hospital admissions. In this report, we present the first patient experience with levosimendan infusion led by CardioMEMS. Case summary A 68-year-old man with HF and reduced EF with more than 20 hospitalizations for exacerbation of HF was enrolled in our HF Clinic from October 2017. Echocardiogram showed a dilated left ventricle with severely reduced EF (29%) and increased pulmonary artery systolic pressure (40 mmHg). From October 2017 to May 2019, the patient went through numerous hospitalizations, despite optimal medical therapy; subsequently, was adopted a strategy of levosimendan infusions guided by CardioMEMS. Levosimendan infusions improved haemodynamic and pressure profiles. The patient was monitored daily by CardioMEMS, and from June to December 2019, he had only two hospitalizations scheduled for levosimendan infusion and none for HF exacerbation. Discussion Our case supports the combination of CardioMEMS and levosimendan for the optimal management of patients with advanced HF. These results further strengthen the development of a randomized clinical trial to demonstrate the clinical usefulness of this device in combination with the levosimendan infusion programme in advanced HF patients

A Multistep Approach to Deal With Advanced Heart Failure: A Case Report on the Positive Effect of Cardiac Contractility Modulation Therapy on Pulmonary Pressure Measured by CardioMEMS

During the last years, the management of heart failure (HF) made substantial progress, focusing on device-based therapies to meet the demands of this complex syndrome. In this case report, we present a multistep approach to deal with HF. Specifically, we report the first patient subjected to the implantation of both Optimizer Smart(R) (Impulse Dynamics Inc., Marlton, NJ, USA) and CardioMEMS devices. A 72-year-old male patient with HF and reduced ejection fraction (HFrEF) was admitted to our cardiology department in January 2021, following a progressive shortening of the time between hospitalizations for levosimendan infusions. Specifically, the patient was monitored daily by CardioMEMS, and a strategy of levosimendan infusions guided by the device had been adopted. He was also a carrier of MitraClips and cardiac resynchronization therapy defibrillator (CRT-D) and had optimized HF medical therapy. In January 2021, the patient implanted Optimizer Smart(R) device for cardiac contractility modulation (CCM) therapy because of poor response to therapy and elevated pulmonary artery pressure (PAP). CCM significantly reduced PAP values following discharge (systolic PAP 33.67 & PLUSMN; 2.92 vs. 40.6 & PLUSMN; 3.37 mmHg, diastolic PAP 14.5 & PLUSMN; 2.01 vs. 22.5 & PLUSMN; 2.53 mmHg, mean PAP 22.87 & PLUSMN; 2.20 vs. 30.9 & PLUSMN; 2.99 mmHg, HR 60.93 & PLUSMN; 1.53 vs. 80.83 & PLUSMN; 3.66 bpm; p < 0.0001), with persisting effect at 9 months. The usefulness of CCM is objectively demonstrated for the first time by continuous invasive monitoring of PAP by CardioMEMS, which can suggest the correct timing for CCM implantation

Nonylphenol effects on human prostate non tumorigenic cells

Nonylphenol (NP) is an industrial chemical with estrogenic activity both in vivo and in vitro; estrogens play a critical role in the development of prostate and may be the cause of some pathological states, including cancer. In this study we examined the effects of NP on human prostate non tumorigenic epithelial cells (PNT1A) investigating on cell proliferation, interaction with estrogen receptors (ERs) and gene expression of genes involved in prostate diseases. We found that NP affects cell proliferation at 10(-6)M, promoting a cytoplasm-nucleus translocation of ERα and not ERβ, like the natural estrogen 17β-estradiol (E2). Moreover, we showed that NP enhances gene expression of key regulators of cell cycle. Estrogen selective antagonist ICI182780 in part reverted the observed effects of NP. These results confirm the estrogenic activity of NP and suggest that other transduction pathways may be involved in NP action on prostate

A review of the molecular mechanisms underlying the development and progression of cardiac remodeling

Pathological molecular mechanisms involved in myocardial remodeling contribute to alter the existing structure of the heart, leading to cardiac dysfunction. Among the complex signaling network that characterizes myocardial remodeling, the distinct processes are myocyte loss, cardiac hypertrophy, alteration of extracellular matrix homeostasis, fibrosis, defective autophagy, metabolic abnormalities, and mitochondrial dysfunction. Several pathophysiological stimuli, such as pressure and volume overload, trigger the remodeling cascade, a process that initially confers protection to the heart as a compensatory mechanism. Yet chronic inflammation after myocardial infarction also leads to cardiac remodeling that, when prolonged, leads to heart failure progression. Here we review the molecular pathways involved in cardiac remodeling, with particular emphasis on those associated with myocardial infarction. A better understanding of cell signaling involved in cardiac remodeling may support the development of new therapeutic strategies towards the treatment of heart failure and reduction of cardiac complications. We will also discuss data derived from gene therapy approaches for modulating key mediators of cardiac remodeling

A Novel Combination of High-Load Omega-3 Lysine Complex (AvailOm®) and Anthocyanins Exerts Beneficial Cardiovascular Effects

Omega-3 fatty acids have been shown to exert several beneficial effects in the prevention of cardiovascular and cerebrovascular diseases. The objective of the present study was to analyze the effects of a novel high-load omega-3 lysine complex, AvailOm®, its related constituents and a novel mixture of AvailOm® with specific vasoactive anthocyanins on vascular function in mice resistance artery. Pressure myograph was used to perform vascular reactivity studies. Nitric oxide and oxidative stress were assessed by difluorofluorescein diacetate and dihydroethidium, respectively. Increasing doses of AvailOm® exerted a dose-response vasorelaxation via AMPK-eNOS-mediated signaling. Omega-3 Ethyl Ester was identified as the main bioactive derivative of AvailOm®, being capable of inducing vasorelaxant action to the same extent of entire product. The combination of AvailOm® with a mix of potent vasoactive anthocyanins (C3-glu + DP3-glu + Mal3-glu + Mal3-gal + PEO3-gal), strongly protected mesenteric arteries from vascular dysfunction and oxidative stress evoked by oxidized-LDL. These data demonstrate for the first time the direct effects of AvailOm® on resistance arteries. The evidence that the combination of specific vasoactive anthocyanins and AvailOm® further enhanced the vasculoprotective properties of these compounds, may offer new promising perspectives for preventing the onset of cardiovascular and cerebrovascular events

The genetics of exceptional longevity identifies new druggable targets forvascular protection and repair

Therapeutic angiogenesis is a relatively new medical strategy in the field of cardiovascular diseases. The underpinning concept is that angiogenic growth factors or proangiogenic cells could be exploited therapeutically in cardiovascular patients to enhance native revascularization responses to an ischemic insult, thereby accelerating tissue healing. The initial enthusiasm generated by preclinical studies has been tempered by the modest success of clinical trials assessing therapeutic angiogenesis. Similarly, proangiogenic cell therapy has so far not maintained the original promises. Intriguingly, the current trend is to consider regeneration as a prerogative of the youngest organism. Consequentially, the embryonic and foetal models are attracting much attention for clinical translation into corrective modalities in the adulthood. Scientists seem to undervalue the lesson from Mother Nature, e.g. all humans are born young but very few achieve the goal of an exceptional healthy longevity. Either natural experimentation is driven by a supreme intelligence or stochastic phenomena, one has to accept the evidence that healthy longevity is the fruit of an evolutionary process lasting million years. It is therefore extremely likely that results of this natural experimentation are more reliable and translatable than the intensive, but very short human investigation on mechanisms governing repair and regeneration. With this preamble in mind, here we propose to shift the focus from the very beginning to the very end of human life and thus capture the secret of prolonged health span to improve well-being in the adulthood

Bioprosthetic Valve Fracture After TAVR Complicated by Balloon Rupture: Bail-Out TAVR in TAVR in SAVR

Transcatheter aortic valve replacement in surgical aortic valve is a safe and effective procedure to treat patients with failed bioprosthetic surgical valves at high risk for reoperation. Performing bioprosthetic valve fracture has been shown to improve postprocedural hemodynamics of TAVR in surgical aortic valve replacement. However, specific complications related to valve fracture are becoming more common. (Level of Difficulty: Advanced.)