November 10, 2022
PA-20-183 Research Project Grant (Parent R01 Clinical Trial Required)
PA-20-185 NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)
NOT-HL-19-690 NHLBI Limitations on Clinical Trial Applications Submitted to the NIH Parent (R01 Clinical Trial Required) Funding Opportunity Announcement (FOA)
National Heart, Lung, and Blood Institute (NHLBI)
The purpose of this NOSI is to stimulate research on lipoprotein(a) [Lp(a)] and its role in cardiovascular disease (CVD). We encourage multidisciplinary collaborations to conduct basic, preclinical, and mechanistic clinical studies on Lp(a) and CVD.
Lp(a) is composed of a low-density lipoprotein (LDL)-like particle, linked to apolipoprotein(a) [apo(a)]. Apo(a) has many different isoforms and makes Lp(a) a complex lipoprotein. Lp(a) is subject to tight genetic control mostly in the LPA gene encoding apo(a). Patients with elevated Lp(a) levels have an increased risk of CVD, including heart attack, stroke and peripheral arterial disease as well as calcific aortic stenosis (AS). Recent genetic studies indicate that Lp(a) is a causal and independent risk factor for CVD. It is well established that Lp(a) levels differ across different racial and ethnic groups.
Although much progress has been made in Lp(a) field, there are still many unanswered questions such as fundamentally understanding Lp(a) biology and pathophysiology, globally standardized Lp(a) assays, risk and therapy thresholds of Lp(a) in different racial/ethnic groups, Lp(a) in clinical risk prediction, and identification of novel therapeutic targets.
There are several challenges and barriers that have hindered the progress in Lp(a) and CVD field. These may include: 1) the lack of awareness on the large global impact of Lp(a) in CVD. It was only recently that strong evidence for a causal relationship of Lp(a) levels to CVD was emerging from epidemiological, genome-wide association studies, and Mendelian randomization studies; 2) the lack of reliable in vitro cell lines and in vivo animal models. Lp(a) is not present in commonly studied laboratory animals and the structure of Lp(a) is complex and thus makes it difficult to generate appropriate animal models to study Lp(a); 3) the lack of standardized Lp(a) assays. Lp(a) assays have been significantly improved through the years. However, global standardization of Lp(a) assays is still in development; and 4) the lack of specific therapies to lower Lp(a) levels. The recent therapeutic development that targets apo(a) is promising but these are still in different phases of clinical trials.
Thus, this NOSI is intended to facilitate collaborative research on Lp(a) and investigate its role in CVD development.
Selected Research Examples
Research areas of interest include, but are not limited to the following:
Application and Submission Information
This notice applies to due dates on or after February 5, 2023 and subsequent receipt dates through January 7, 2026.
Submit applications for this initiative using one of the following funding opportunity announcements (FOAs) or any reissues of these announcement through the expiration date of this notice.
Note: NHLBI will accept only mechanistic studies that meet the NIH definition of a clinical trial (see NOT-HL-18-662 and NOT-NS-18-011) in response to PA-20-183 NIH Research Project Grant (Parent R01 Clinical Trial Required) and its reissues. For additional information, please see the NHLBI Policy Regarding Submission of Clinical Trial Applications Notice for help in identifying the most appropriate FOA (see NOT-HL-18-611).
All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:
Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.
Lijuan Liu, PhD
National Heart, Lung, and Blood Institute
Division of Cardiovascular Sciences
Peer Review Contact(s)
Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).
Financial/Grants Management Contact(s)
National Heart, Lung, and Blood Institute