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Chronic kidney disease (CKD) stands as a prominent non-communicable ailment, significantly impacting life expectancy. Physiopathology stands mainly upon the triangle represented by parathormone–Vitamin D–Fibroblast Growth Factor-23. Parathormone (PTH), the key hormone in mineral homeostasis, is one of the less easily modifiable parameters in CKD; however, it stands as a significant marker for assessing the risk of complications. The updated “trade-off hypothesis” reveals that levels of PTH spike out of the normal range as early as stage G2 CKD, advancing it as a possible determinant of systemic damage. The present review aims to review the effects exhibited by PTH on several organs while linking the molecular mechanisms to the observed actions in the context of CKD. From a diagnostic perspective, PTH is the most reliable and accessible biochemical marker in CKD, but its trend bears a higher significance on a patient’s prognosis rather than the absolute value. Classically, PTH acts in a dichotomous manner on bone tissue, maintaining a balance between formation and resorption. Under the uremic conditions of advanced CKD, the altered intestinal microbiota majorly tips the balance towards bone lysis. Probiotic treatment has proven reliable in animal models, but in humans, data are limited. Regarding bone status, persistently high levels of PTH determine a reduction in mineral density and a concurrent increase in fracture risk. Pharmacological manipulation of serum PTH requires appropriate patient selection and monitoring since dangerously low levels of PTH may completely inhibit bone turnover. Moreover, the altered mineral balance extends to the cardiovascular system, promoting vascular calcifications. Lastly, the involvement of PTH in the Renin–Angiotensin–Aldosterone axis highlights the importance of opting for the appropriate pharmacological agent should hypertension develop.

One of the essential regulators of arterial blood pressure, the renin-angiotensin-aldosterone system (RAAS) seems to be one of the most complex mechanisms in the human body. Since the discovery of its key components and their actions, new substances and functions are still being unraveled. The main pathway begins with the secretion of renin in the kidney and culminates with the synthesis of angiotensin II (Ang II)—a strong vasoconstrictor—thanks to the angiotensin-converting enzyme (ACE). Research conducted in 2000 identified another enzyme, named ACE2, that converts Ang II into Ang-(1–7), a heptapeptide with opposing effects to those of Ang II: vasodilation and anti-inflammatory properties. This particular enzyme became of paramount importance during the last two decades, as a result of the confrontation of the human race with life-threatening epidemics. Multiple studies have been performed in order to uncover the link between ACE2 and human coronaviruses, the results of which we systemized in order to create an overview of the pathogenic mechanism. Human coronaviruses, such as SARS-CoV and SARS-CoV-2, attach to ACE2 via their spike proteins (S), causing the destruction of the enzyme. Because ACE2 limits the production of Ang II (by converting it into Ang-(1–7)), its destruction leads to a dysregulated inflammatory response. The purpose of this review is to decipher the complex pathophysiological mechanisms underlying the multiorgan complications (oral, cardiac, pulmonary, systemic) that appear as a result of the interaction of the SARS CoV-2 virus with the angiotensin-converting enzyme type 2.

Calcific aortic valve disease (CAVD) is a major cause of cardiovascular mortality and morbidity, with increased prevalence and incidence. The underlying mechanisms behind CAVD are complex, and are mainly illustrated by inflammation, mechanical stress (which induces prolonged aortic valve endothelial dysfunction), increased oxidative stress (OS) (which trigger fibrosis), and calcification of valve leaflets. To date, besides aortic valve replacement, there are no specific pharmacological treatments for CAVD. In this review, we describe the mechanisms behind aortic valvular disease, the involvement of OS as a fundamental element in disease progression with predilection in AS, and its two most frequent etiologies (calcific aortic valve disease and bicuspid aortic valve); moreover, we highlight the potential of OS as a future therapeutic target.

Arterial hypertension (HTN) is one of the most prevalent entities globally, characterized by increased incidence and heterogeneous pathophysiology. Among possible etiologies, oxidative stress (OS) is currently extensively studied, with emerging evidence showing its involvement in endothelial dysfunction and in different cardiovascular diseases (CVD) such as HTN, as well as its potential as a therapeutic target. While there is a clear physiological equilibrium between reactive oxygen species (ROS) and antioxidants essential for many cellular functions, excessive levels of ROS lead to vascular cell impairment with decreased nitric oxide (NO) availability and vasoconstriction, which promotes HTN. On the other hand, transcription factors such as nuclear factor erythroid factor 2-related factor 2 (Nrf2) mediate antioxidant response pathways and maintain cellular reduction–oxidation homeostasis, exerting protective effects. In this review, we describe the relationship between OS and hypertension-induced endothelial dysfunction and the involvement and therapeutic potential of Nrf2 in HTN.

Aim: Activation of the sympathetic nervous system is common in resistant hypertension (RHT) and also in chronic kidney disease (CKD), a prevalent condition among resistant hypertensives. However, renal nerve ablation lowers blood pressure (BP) only in some patients with RHT. The influence of loss of nephrons per se on the antihypertensive response to renal denervation (RDNx) is unclear and was the focus of this study.Methods: Systemic hemodynamics and sympathetically mediated low frequency oscillations of systolic BP were determined continuously from telemetrically acquired BP recordings in rats before and after surgical excision of ∼80% of renal mass and subsequent RDNx.Results: After reduction of renal mass, rats fed a high salt (HS) diet showed sustained increases in mean arterial pressure (108 ± 3 mmHg to 128 ± 2 mmHg) and suppression of estimated sympathetic activity (∼15%), responses that did not occur with HS before renal ablation. After denervation of the remnant kidney, arterial pressure fell (to 104 ± 4 mmHg), estimated sympathetic activity and heart rate (HR) increased concomitantly, but these changes gradually returned to pre-denervation levels over 2 weeks of follow up. Subsequently, sympathoinhibition with clonidine did not alter arterial pressure while significantly suppressing estimated sympathetic activity and HR.Conclusion: These results indicate that RDNx does not chronically lower arterial pressure in this model of salt-sensitive hypertension associated with substantial nephron loss, but without ischemia and increased sympathetic activity, thus providing further insight into conditions likely to impact the antihypertensive response to renal-specific sympathoinhibition in subjects with CKD.

Abstract This study aimed to investigate the effects of chronic sympathoinhibition on glucose uptake by the myocardium and by the skeletal muscle in an animal model of obesity associated with leptin signaling deficiency. 6 obese Zucker rats (OZR) and 6 control Lean Zucker rats (LZR) were studied during basal conditions, chronic clonidine administration (30 days, 300 µg/kg), and washout recovery period. Glucose uptake in the myocardium and in the skeletal muscle was measured using positron emission tomography (PET) and 2-[18F] fluoro-2-deoxy-D-glucose ([18F]FDG). The standardized uptake value (SUV) corrected for blood glucose was used for the semi-quantitative analysis. Body weight, food and water intake, blood glucose concentration, blood pressure variability as an index of sympathetic activity and hemodynamic parameters such as mean arterial blood pressure (MAP), systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) were analyzed. Myocardial glucose uptake was significantly lower during basal conditions in OZR versus LZR. In both OZR and LZR, chronic clonidine significantly reduced myocardial glucose uptake and hemodynamic variables (such as MAP, SBP, DBP, HR), and sympathetic activity (SA). [18F]FDG skeletal muscle uptake did not significantly differ in OZR versus LZR. Our findings indicate that cardiac glucose metabolism is reduced in obesity presumably in relation with the level of sympathetic activation.

Background and Objectives: Chronic heart failure (CHF) caused by ischemic heart disease (IHD) is the leading cause of death worldwide and presents significant health challenges. Effective management of IHD requires prevention, early detection, and treatment to improve patient outcomes. This study aims to expand the diagnostic utility of various 24 h Holter ECG parameters, such as T-wave alternans (TWA), late ventricular potentials (LVPs), and heart rate variability (HRV) in patients with CHF caused by IHD. Additionally, we seek to explore the association between these parameters and other comorbid conditions affecting the prognosis of CHF patients. Materials and Methods: We conducted a prospective case–control study with 150 patients divided into two subgroups: 100 patients with CHF caused by IHD, and 50 patients in the control group. Data included medical history, physical examination, laboratory tests, echocardiography, and 24 h Holter monitoring. Results: Our comparative analysis demonstrated that both TWA and LVPs were significantly higher in patients with CHF compared to the control group (p < 0.01), indicating increased myocardial electrical vulnerability in CHF patients. Both time and frequency-domain HRV parameters were significantly lower in the CHF group. However, the ratio of NN50 to the total count of NN intervals (PNN50) showed a borderline significance (p = 0.06). While the low-frequency (LF) domain was significantly lower in CHF patients, the high-frequency (HF) domain did not differ significantly between groups. Acceleration and deceleration capacities were also significantly altered in CHF patients. Categorizing CHF patients by left ventricular ejection fraction (LVEF) revealed that the mean of the 5-min normal-to-normal intervals over the complete recording (SDNN Index) was significantly higher in patients with LVEF ≥ 50% compared to those with CHF with reduced EF and CHF with mildly reduced EF (p < 0.001), whereas the other HRV parameters showed no significant differences among the groups. Conclusions: Holter ECG parameters can become a reliable tool in the assessment of patients with CHF. The integration of multiple Holter ECG parameters, such as TWA, LVPs, and HRV, can significantly enhance the diagnostic assessment of CHF caused by IHD. This comprehensive approach allows for a more nuanced understanding of the patient’s condition and potential outcomes.

Background and Objective: In the landscape of heart failure, non-cardiac comorbidities represent a formidable challenge, imparting adverse prognostic implications. Holter ECG monitoring assumes a supplementary role in delineating myocardial susceptibility and autonomic nervous system dynamics. This study aims to explore the potential correlation between Holter ECG parameters and comorbidities in individuals with ischemic cardiomyopathy experiencing heart failure (HF), with a particular focus on the primary utility of these parameters as prognostic indicators. Materials and Methods: In this prospective inquiry, a cohort of 60 individuals diagnosed with heart failure underwent stratification into subgroups based on the presence of comorbidities, including diabetes, chronic kidney disease, obesity, or hyperuricemia. Upon admission, a thorough evaluation of all participants encompassed echocardiography, laboratory panel analysis, and 24 h Holter monitoring. Results: Significant associations were uncovered between diabetes and unconventional physiological indicators, specifically the Triangular index (p = 0.035) and deceleration capacity (p = 0.002). Pertaining to creatinine clearance, notable correlations surfaced with RMSSD (p = 0.026), PNN50 (p = 0.013), and high-frequency power (p = 0.026). An examination of uric acid levels and distinctive Holter ECG patterns unveiled statistical significance, particularly regarding the deceleration capacity (p = 0.045). Nevertheless, in the evaluation of the Body Mass Index, no statistically significant findings emerged concerning Holter ECG parameters. Conclusions: The identified statistical correlations between non-cardiac comorbidities and patterns elucidated in Holter ECG recordings underscore the heightened diagnostic utility of this investigative modality in the comprehensive evaluation of individuals grappling with HF. Furthermore, we underscore the critical importance of the thorough analysis of Holter ECG recordings, particularly with regard to subtle and emerging parameters that may be overlooked or insufficiently acknowledged.

Myocardial ischemia is a pathophysiological state characterized by inadequate perfusion of the myocardium, resulting in an imbalance between myocardial oxygen demand and supply. It is most commonly caused by coronary artery disease, in which atherosclerotic plaques lead to luminal narrowing and reduced blood flow to the heart. Myocardial ischemia can manifest as angina pectoris or silent myocardial ischemia and can progress to myocardial infarction or heart failure if left untreated. Diagnosis of myocardial ischemia typically involves a combination of clinical evaluation, electrocardiography and imaging studies. Electrocardiographic parameters, as assessed by 24 h Holter ECG monitoring, can predict the occurrence of major adverse cardiovascular events in patients with myocardial ischemia, independent of other risk factors. The T-waves in patients with myocardial ischemia have prognostic value for predicting major adverse cardiovascular events, and their electrophysiological heterogeneity can be visualized using various techniques. Combining the electrocardiographic findings with the assessment of myocardial substrate may offer a better picture of the factors that can contribute to cardiovascular death.

Despite the improvements in the treatment of coronary artery disease (CAD) and acute myocardial infarction (MI) over the past 20 years, ischemic heart disease (IHD) continues to be the most common cause of heart failure (HF). In clinical trials, over 70% of patients diagnosed with HF had IHD as the underlying cause. Furthermore, IHD predicts a worse outcome for patients with HF, leading to a substantial increase in late morbidity, mortality, and healthcare costs. In recent years, new pharmacological therapies have emerged for the treatment of HF, such as sodium-glucose cotransporter-2 inhibitors, angiotensin receptor-neprilysin inhibitors, selective cardiac myosin activators, and oral soluble guanylate cyclase stimulators, demonstrating clear or potential benefits in patients with HF with reduced ejection fraction. Interventional strategies such as cardiac resynchronization therapy, cardiac contractility modulation, or baroreflex activation therapy might provide additional therapeutic benefits by improving symptoms and promoting reverse remodeling. Furthermore, cardiac regenerative therapies such as stem cell transplantation could become a new therapeutic resource in the management of HF. By analyzing the existing data from the literature, this review aims to evaluate the impact of new HF therapies in patients with IHD in order to gain further insight into the best form of therapeutic management for this large proportion of HF patients.

The endocannabinoid system (ECS) dynamically regulates many aspects of mammalian physiology. ECS has gained substantial interest since growing evidence suggests that it also plays a major role in several pathophysiological conditions due to its ability to modulate various underlying mechanisms. Furthermore, cannabinoids, as components of the cannabinoid system (CS), have proven beneficial effects such as anti-inflammatory, immunomodulatory, neuromodulatory, antioxidative, and cardioprotective effects. In this comprehensive review, we aimed to describe the complex interaction between CS and most common age-related diseases such as neuro-degenerative, oncological, skeletal, and cardiovascular disorders, together with the potential of various cannabinoids to ameliorate the progression of these disorders. Since chronic inflammation is postulated as the pillar of all the above-mentioned medical conditions, we also discuss in this paper the potential of CS to ameliorate aging-associated immune system dysregulation.

Heart failure (HF) is a progressively deteriorating medical condition that significantly reduces both the patients’ life expectancy and quality of life. Even though real progress was made in the past decades in the discovery of novel pharmacological treatments for HF, the prevention of premature deaths has only been marginally alleviated. Despite the availability of a plethora of pharmaceutical approaches, proper management of HF is still challenging. Thus, a myriad of experimental and clinical studies focusing on the discovery of new and provocative underlying mechanisms of HF physiopathology pave the way for the development of novel HF therapeutic approaches. Furthermore, recent technological advances made possible the development of various interventional techniques and device-based approaches for the treatment of HF. Since many of these modern approaches interfere with various well-known pathological mechanisms in HF, they have a real ability to complement and or increase the efficiency of existing medications and thus improve the prognosis and survival rate of HF patients. Their promising and encouraging results reported to date compel the extension of heart failure treatment beyond the classical view. The aim of this review was to summarize modern approaches, new perspectives, and future directions for the treatment of HF.

Cardiovascular diseases represent the leading cause of mortality worldwide, with recent epidemiological studies revealing an increasing trend of prevalence and incidence globally. Among cardiovascular disorders, both arterial and venous thrombosis and particularly their acute life-threating complications such as ischemic stroke, acute myocardial infarction, deep venous thrombosis and pulmonary embolism are responsible for more than 25% of all deaths worldwide. The modern approach following progresses in anticoagulant, thrombolytic and antiaggregant therapies has significantly improved the prognoses of these conditions in the last past decades. However, several challenges still remain such as achieving the optimal drug concentration at the injured site, reducing the shortcomings of drug resistance and the incidence of life-threatening hemorrhages. Nanomedicine is a well-known field of medicine in which atomic and molecular structures ranging between 0.1–100 nm are used in various domains due to their specific mechanical, electrical, thermal and magnetic properties. Recent experimental and clinical evidence have shown that nanotechnology could be a safe, effective and an appealing approach for various non-cardiovascular and cardiovascular diseases such as thromboembolic conditions. In this review, we have described the most promising nanotechnology-based approaches not only for the diagnosis, but also for the treatment of vascular thrombotic diseases.

(1) Background: Collagen is the main component of the connective tissue, playing an important role in the histological architecture and function of living organisms. Targeted therapy and improved imaging diagnosis can be obtained through collagen-binding nanoparticles that concentrate in the extracellular matrix. (2) Methods: We performed a scoping review of studies that analyzed the binding capacity of collagen-targeting nanoparticles. The search algorithm and inclusion criteria were based on PRISMA and ARRIVE guidelines. (3) Results: Fourteen studies matched all the inclusion criteria. All studies analyzed the distribution of nanoparticles in the collagen matrix, either by using collagen-targeting nanoparticles or by using unmodified ones. Most studies used collagen-binding nanoparticles for vascular research to target sites of endothelial injury, atherosclerotic plaques, or myocardial infarction. Two studies targeted the exposed collagen in models of liver fibrosis. (4) Conclusions: Our review summarizes the current literature on the methods and outcomes of using nanoparticles to target collagen. The studies reveal that there is high applicability for collagen-binding nanoparticles in cardiac or hepatic pathology and they could prove useful for targeted therapy of neoplastic lesions, which show an abundance of stromal collagen.

In the field of oncology, a lot of improvements in nanotechnology creates support for better diagnosis and therapeutic opportunities, and due to their physical and chemical properties, gold nanoparticles are highly applicable. We performed a literature review on the studies engaging the usage of gold nanoparticles on murine models with a focus on the type of the carrier, the chemotherapy drug, the target tumoral tissue and outcomes. We identified fifteen studies that fulfilled our search criteria, in which we analyzed the synthesis methods, the most used chemotherapy conjugates of gold nanoparticles in experimental cancer treatment, as well as the improved impact on tumor size and system toxicity. Due to their intrinsic traits, we conclude that chemotherapy conjugates of gold nanoparticles are promising in experimental cancer treatment and may prove to be a safer and improved therapy option than current alternatives.

Cardiovascular diseases (CVDs) represent the most important epidemic of our century, with more than 37 million patients globally. Furthermore, CVDs are associated with high morbidity and mortality, and also increased hospitalization rates and poor quality of life. Out of the plethora of conditions that can lead to CVDs, atherosclerosis and ischemic heart disease are responsible for more than 2/3 of the cases that end in severe heart failure and finally death. Current therapy strategies for CVDs focus mostly on symptomatic benefits and have a moderate impact on the underlying physiopathological mechanisms. Modern therapies try to approach different physiopathological pathways such as reduction of inflammation, macrophage regulation, inhibition of apoptosis, stem-cell differentiation and cellular regeneration. Recent technological advances make possible the development of several nanoparticles used not only for the diagnosis of cardiovascular diseases, but also for targeted drug delivery. Due to their high specificity, nanocarriers can deliver molecules with poor pharmacokinetics and dynamics such as: peptides, proteins, polynucleotides, genes and even stem cells. In this review we focused on the applications of nanoparticles in the diagnosis and treatment of ischemic heart failure and atherosclerosis.

Our aim was to develop a new experimental model for in vivo hyperthermia using non-directional microwaves, applicable to small experimental animals. We present an affordable approach for targeted microwave heat delivery to an isolated liver lobe in rat, which allows rapid, precise and stable tissue temperature control.A new experimental model is proposed. We used a commercial available magnetron generating 2450 MHz, with 4.4V and 14A in the filament and 4500V anodic voltage. Modifications were required in order to adjust tissue heating such as to prevent overheating and to allow for fine adjustments according to real-time target temperature. The heating is controlled using a virtual instrument application implemented in LabView® and responds to 0.1° C variations in the target. Ten healthy adult male Wistar rats, weighing 250-270 g were used in this study. The middle liver lobe was the target for controlled heating, while the rest of the living animal was protected.In vivo microwave delivery using our experimental setting is safe for the animals. Target tissue temperature rises from 30°C to 40°C with 3.375°C / second (R2 = 0.9551), while the increment is lower it the next two intervals (40-42°C and 42-44°C) with 0.291°C/ s (R2 = 0.9337) and 0.136°C/ s (R2 = 0.7894) respectively, when testing in sequences. After reaching the desired temperature, controlled microwave delivery insures a very stable temperature during the experiments.We have developed an inexpensive and easy to manufacture system for targeted hyperthermia using non-directional microwave radiation. This system allows for fine and stable temperature adjustments within the target tissue and is ideal for experimental models testing below or above threshold hyperthermia.