Molecular Pathways in Pulmonary Arterial Hypertension

Pulmonary arterial hypertension is a multifactorial, chronic disease process that leads to pulmonary arterial endothelial dysfunction and smooth muscular hypertrophy, resulting in impaired pliability and hemodynamics of the pulmonary vascular system, and consequent right ventricular dysfunction. Existing treatments target limited pathways with only modest improvement in disease morbidity, and little or no improvement in mortality. Ongoing research has focused on the molecular basis of pulmonary arterial hypertension and is going to be important in the discovery of new treatments and genetic pathways involved. This review focuses on the molecular pathogenesis of pulmonary arterial hypertension

Strategizing Drug Therapies in Pulmonary Hypertension for Improved Outcomes

Pulmonary hypertension (PH) is characterized by a resting mean pulmonary artery pressure (PAP) of 20 mmHg or more and is a disease of multiple etiologies. Of the various types of PH, pulmonary arterial hypertension (PAH) is characterized by elevated resistance in the pulmonary arterial tree. It is a rare but deadly disease characterized by vascular remodeling of the distal pulmonary arteries. This paper focuses on PAH diagnosis and management including current and future treatment options. Over the last 15 years, our understanding of this progressive disease has expanded from the concept of vasoconstrictive/vasodilatory mismatch in the pulmonary arterioles to now a better appreciation of the role of genetic determinants, numerous cell signaling pathways, cell proliferation and apoptosis, fibrosis, thrombosis, and metabolic abnormalities. While knowledge of its pathophysiology has expanded, the majority of the treatments available today still modulate the same three vasodilatory pathways that have been targeted for over 30 years (endothelin, nitric oxide, and prostacyclin). While modifying these pathways may help improve symptoms and quality of life, none of these directly modify the underlying disease pathogenesis. However, there are now studies ongoing with new drugs that can prevent or reverse these underlying causes of PAH. This review discusses the evidence base for the current treatment algorithms for PAH, as well as discusses novel therapies in development

Role of lipid-lowering therapy in peripheral artery disease

Atherosclerosis is a multifactorial, lipoprotein-driven condition that leads to plaque formation within the arterial tree, leading to subsequent arterial stenosis and thrombosis that accounts for a large burden of cardiovascular morbidity and mortality globally. Atherosclerosis of the lower extremities is called peripheral artery disease and is a major cause of loss in mobility, amputation, and critical limb ischemia. Peripheral artery disease is a common condition with a gamut of clinical manifestations that affects an estimated 10 million people in the United States of America and 200 million people worldwide. The role of apolipoprotein B-containing lipoproteins, such as LDL and remnant lipoproteins in the development and progression of atherosclerosis, is well-established. The focus of this paper is to review existing data on lipid-lowering therapies in lower extremity atherosclerotic peripheral artery disease

Dyslipidemia in human immunodeficiency virus disease: JACC review topic of the week

The advent of newer and better tolerated antiretroviral therapy has progressively shortened the life expectancy gap between people living with HIV (PWH) and the general population. However, in this aging cohort, cardiovascular disease is now a significant cause of morbidity and mortality despite advances in cardiac care. Therefore, it is critical to assess and treat all cardiovascular disease risk factors, including dyslipidemia, early and aggressively in PWH. Data are not as robust regarding the pathogenesis and management of dyslipidemia in PWH, with most evidence being extrapolated from the general uninfected population. In this review the authors describe the current understanding of the pathophysiology of HIV and antiretroviral therapy-induced dyslipidemia, and the approach to risk assessment and management, given that drug-drug interactions remain an important consideration in this population