Natriuretic Peptides in the Cardiovascular System. Multifaceted Roles in Physiology, Pathology and Therapeutics

The natriuretic peptides (NPs) family includes a class of hormones and their receptors needed for the physiological control of cardiovascular functions. The discovery of NPs provided a fundamental contribution into our understanding of the physiological regulation of blood pressure, and of heart and kidney functions. NPs have also been implicated in the pathogenesis of several cardiovascular diseases (CVDs), including hypertension, atherosclerosis, heart failure, and stroke. A fine comprehension of the molecular mechanisms dependent from NPs and underlying the promotion of cardiovascular damage has contributed to improve our understanding of the molecular basis of all major CVDs. Finally, the opportunity to target NPs in order to develop new therapeutic tools for a better treatment of CVDs has been developed over the years. The current Special Issue of the Journal covers all major aspects of the molecular implications of NPs in physiology and pathology of the cardiovascular system, including NP-based therapeutic approaches

Synergistic effects of cardiac resynchronization therapy and drug up-titration in heart failure. is this enough?

This editorial refers to ‘Optimization of heart failure medication after cardiac resynchronization therapy and the impact on long-term survival’, by C.T. Witt et al., on page 18

Inflammatory residual risk. An emerging target to reduce cardiovascular disease

Cardiovascular Residual Risk and Cardiovascular Preventio

Is early and fast blood pressure control important in hypertension management?

Control of blood pressure (BP) in hypertension is recognized as a key measure in the management of cardiovascular (CV) risk and is a cornerstone of preventive strategies. It is not defined, however, whether an initiation of the antihypertensive treatment in the early stages of hypertension (such as prehypertension or high-normal BP), may bring benefits for the long-term prevention of CV events. In addition, it has not been thoroughly addressed the issue whether achievement of a prompt BP reduction in hypertensive patients may contribute to reduce CV damage and events. The aim of this article is to critically examine data from studies exploring these important questions. Our conclusion is that the available evidence, though not very extensive, supports the prevailing benefits associated with early BP control. We also discuss the therapeutic strategies to achieve early control of BP. Finally, we believe that this aspect deserves to be more thoroughly addressed in upcoming international guidelines

Integrated preclinical cardiovascular prevention: a new paradigm to face growing challenges of cardiovascular disease

Cardiovascular disease (CVD) still represents the leading cause of mortality and morbidity worldwide. Despite considerable improvements in the prognosis of CVD and the significant reduction of CVD mortality obtained during the past half century, patients developing CVD, even though satisfactorily treated, still carry coronary artery disease and remain at risk for advanced CVD. Thus, the healthcare and socioeconomic burden linked to CVD remains high. As a result, more effective CVD prevention strategies remain crucial. 'Population strategies' and 'high-risk' approaches both have limitations and have often been viewed as alternative solutions. This persistent dualism could be overcome with the promotion of integrated prevention strategies based on a systematic evaluation of the total risk of disease, at both a population and an individual level. New approaches are also needed to reach people earlier in the course of the vascular disease and, possibly, to prevent risk factors and reduce CVD clinical manifestation

Blood pressure control versus atrial fibrillation management in stroke prevention

Hypertension is one of the major risk factors for atrial fibrillation which in turn is the most prevalent concomitant condition in hypertensive patients. While both these pathological conditions are independent risk factors for stroke, the association of hypertension and atrial fibrillation increases the incidence of disabling strokes. Moreover, documented or silent atrial fibrillation doubles the rate of cardiovascular death. Lowering blood pressure is strongly recommended, particularly for primary stroke prevention. However, a relatively small percentage of hypertensive patients still achieve the recommended blood pressure goals. The management of atrial fibrillation with respect to stroke prevention is changing. New oral anticoagulants represent a major advancement in long-term anticoagulation therapy in non valvular atrial fibrillation. They have several benefits over warfarin, including improved adherence to the anticoagulation therapy. This is an important issue since non-adherence to stroke prevention medications is a risk factor for first and recurrent strokes

Natriuretic peptides and cardio-renal disease

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Hypertension in the elderly. Which are the blood pressure threshold values?

Managing blood pressure is often difficult in the elderly, not only because of comorbidities, but also due to vascular remodelling and the changes in the renal and endocrine physiology. The structural and functional arterial modifications lead to impaired vessel’s compliance and increased systolic blood pressure (SBP), often with reduction of diastolic blood pressure (DBP)

Molecular Implications of natriuretic peptides in the protection from hypertension and target organ damage development

The pathogenesis of hypertension, as a multifactorial trait, is complex. High blood pressure levels, in turn, concur with the development of cardiovascular damage. Abnormalities of several neurohormonal mechanisms controlling blood pressure homeostasis and cardiovascular remodeling can contribute to these pathological conditions. The natriuretic peptide (NP) family (including ANP (atrial natriuretic peptide), BNP (brain natriuretic peptide), and CNP (C-type natriuretic peptide)), the NP receptors (NPRA, NPRB, and NPRC), and the related protease convertases (furin, corin, and PCSK6) constitute the NP system and represent relevant protective mechanisms toward the development of hypertension and associated conditions, such as atherosclerosis, stroke, myocardial infarction, heart failure, and renal injury. Initially, several experimental studies performed in different animal models demonstrated a key role of the NP system in the development of hypertension. Importantly, these studies provided relevant insights for a better comprehension of the pathogenesis of hypertension and related cardiovascular phenotypes in humans. Thus, investigation of the role of NPs in hypertension offers an excellent example in translational medicine. In this review article, we will summarize the most compelling evidence regarding the molecular mechanisms underlying the physiological and pathological impact of NPs on blood pressure regulation and on hypertension development. We will also discuss the protective effect of NPs toward the increased susceptibility to hypertensive target organ damage

A ‘Once-and-Done’ Approach to the Lifelong Reduction of Elevated Cholesterol

Key points CRISPR (clustered regularly interspaced short palindromic repeats)-related technologies are emerging therapeutic strategies to induce DNA modifications in humans. In this regard, gene editing of proprotein convertase subtilisin/kexin type 9 (PCSK9) might represent a promising approach for the prevention of coronary heart disease (CHD). The present study1 investigates the impact of a single-nucleotide PCSK9 loss-of-function mutation by CRISPR adenine base editors (ABE) on low-density lipoprotein cholesterol (LDL-C) levels in non-human primates. To introduce a precise single-nucleotide PCSK9 loss-of-function mutation, a CRISPR ABE was delivered in macaques using lipid nanoparticles (LNPs). Adenine base editors of PCSK9 was confirmed in primary human hepatocytes, primary monkey hepatocytes, and mice. In vivo CRISPR ABE delivery led to a near-complete knockdown of PCSK9 in the liver after a single infusion of LNPs, with concomitant reductions in blood levels of PCSK9 and LDL-C of ∼90% and 60%, respectively. These changes were sustained for at least 8 months after a single-dose treatment. No relevant side effects were observed in the animals treated with a CRISPR editor-based strategy. Off-target gene editing was found at only one site in macaque liver, whereas no off-target editing was found in human hepatocytes