HIF Activation Against CVD in CKD: Novel Treatment Opportunities

Seminars in Nephrology
Tetsuhiro Tanaka, Kai-Uwe Eckardt

Abstract

Cardiovascular disease is a common and serious complication in patients with chronic kidney disease (CKD). One of the fundamental functions of the cardiovascular system is oxygen delivery, therefore cardiovascular disease inherently is linked to insufficient tissue oxygenation. Advances in our knowledge of cellular oxygen sensing by a family of prolyl hydroxylases (PHDs) and their role in regulating hypoxia-inducible factors (HIFs) have led to the discovery of PHD inhibitors as HIF stabilizers. Several small-molecule PHD inhibitors are currently in clinical trials for the treatment of anemia in CKD. An additional advantage of PHD inhibition may be found in the potential impact on cardiovascular consequences associated with CKD. Several preclinical studies have suggested a potential benefit of HIF activation in myocardial infarction, cardiac remodeling, atherosclerosis, and peripheral artery disease. Ameliorating glucose and lipid metabolism and lowering blood pressure may also contribute to cardiovascular protection. On the other hand, the broad spectrum of HIF-dependent functions also may include unwanted side effects. Clinical application of PHD inhibitors therefore necessitates careful evaluation of the net systemic effect o...Continue Reading

Citations

Nov 8, 2018·Blood·Guenter WeissLawrence T Goodnough
Mar 8, 2019·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Francesco Locatelli, Lucia Del Vecchio
Dec 17, 2019·American Journal of Physiology. Renal Physiology·Lisa UchidaMasaomi Nangaku
Jul 28, 2020·American Journal of Physiology. Renal Physiology·Yongzhen ZhaoJian-Xiong Chen
Nov 3, 2020·Virulence·Antonia ReyesPablo A González
Jul 13, 2021·Cardiology Clinics·Matthew J Tunbridge, Alan G Jardine
Aug 1, 2021·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·Jay B WishJeffrey S Berns

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cardiovascular Disease Pathophysiology

Cardiovascular disease involves several different processes that contribute to the pathological mechanism, including hyperglycemia, inflammation, atherosclerosis, hypertension and more. Vasculature stability plays a critical role in the development of the disease. Discover the latest research on cardiovascular disease pathophysiology here.

Anemia

Anemia develops when your blood lacks enough healthy red blood cells. Anemia of inflammation (AI, also called anemia of chronic disease) is a common, typically normocytic, normochromic anemia that is caused by an underlying inflammatory disease. Here is the latest research on anemia.

Cardiac Remodeling

Cardiac remodeling in response to a myocardial infarction is characterized by progressive ventricular dilatation, cardiac hypertrophy, fibrosis, and deterioration of cardiac performance. Discover the latest research on Cardiac Remodeling here.

Atherosclerosis Disease Progression

Atherosclerosis is the buildup of plaque on artery walls, causing stenosis which can eventually lead to clinically apparent cardiovascular disease. Find the latest research on atherosclerosis disease progression here.

Cardiomyopathy

Cardiomyopathy is a disease of the heart muscle, that can lead to muscular or electrical dysfunction of the heart. It is often an irreversible disease that is associated with a poor prognosis. There are different causes and classifications of cardiomyopathies. Here are the latest discoveries pertaining to this disease.